Open Access
Translator Disclaimer
24 April 2015 Mechanism of Cytoplasmic mRNA Translation
Karen S. Browning, Julia Bailey-Serres
Author Affiliations +
Abstract

Protein synthesis is a fundamental process in gene expression that depends upon the abundance and accessibility of the mRNA transcript as well as the activity of many protein and RNA-protein complexes. Here we focus on the intricate mechanics of mRNA translation in the cytoplasm of higher plants. This chapter includes an inventory of the plant translational apparatus and a detailed review of the translational processes of initiation, elongation, and termination. The majority of mechanistic studies of cytoplasmic translation have been carried out in yeast and mammalian systems. The factors and mechanisms of translation are for the most part conserved across eukaryotes; however, some distinctions are known to exist in plants. A comprehensive understanding of the complex translational apparatus and its regulation in plants is warranted, as the modulation of protein production is critical to development, environmental plasticity and biomass yield in diverse ecosystems and agricultural settings.

INTRODUCTION

Plant growth and function requires highly regulated spatial and temporal regulation of gene expression. The decoding of the mRNA into a polypeptide chain (protein) by the ribosome is a key step in the regulatory continuum from gene to protein to phenotype. The process of translation requires many RNAs, the messenger RNA (mRNA) transcript, transfer RNAs (tRNAs) and the ribosomal RNAs (rRNAs) of the ribosome as well as scores of soluble protein factors that function either as individual proteins or in multi-subunit complexes. The decoding of mRNA into a polymer of amino acids is a very ancient process, such that the machine for this process, the two-subunit ribosome, is conserved across all forms of life on Earth. The three basic phases of the process of translation — initiation, elongation and termination — are also generally conserved. Consequentially, many components of the complex apparatus involved are recognizable across phyla, especially across the plant, fungal and animal kingdoms. Despite this conservation of the basic chemistry and process of protein synthesis, nature has evolved many ways of starting the first phase, known as initiation. The second phase known as elongation, in which additional amino acids are covalently added to the polypeptide, and the third phase known as termination that completes the process are much more preserved across all kingdoms. Eubacteria have three proteins known as initiation factors to unite the mRNA, the initiator tRNA (usually tRNAi Met) and the small subunit of the ribosome and assemble them with the large subunit of the ribosome to commence the elongation process. Archaea and eukaryotes have expanded this machinery to include 10 or more proteins or protein complexes, although Archea lack the eIF3 and eIF4 families found in eukaryotes. In addition, a number of “flourishes” have been added to the nuclear-encoded eukaryotic mRNA such as a 5′-m7GpppN cap structure at the 5′ end and a stretch of adenine residues, the poly(A) tail at the 3′ end. These features are added in the nucleus during transcription and are important in transcript stability during the journey from nucleus to cytoplasm and the lifetime of the mRNA. The translational apparatus has evolved to use these added mRNA features to facilitate the process of initiation in the cytoplasm. It is also thought that the role of the extended cohort of initiation factors in eukaryotes is to participate in exquisitely complicated schemes to regulate the process. What could be more important to a cell than the synthesis of the proteins that catalyze the chemistry of metabolism to make the energy for cell growth, division and function? It is therefore not surprising that the plant translational apparatus and its regulation varies from other eukaryotic organisms due to the specialized cellular biochemistry, developmental complexity and environmental plasticity that confers survival and reproduction centered around the capture of light energy and the conversion to chemical energy, i.e., photosynthesis. Another chapter of The Arabidopsis Book evaluates the regulation of translation of cytoplasmic mRNAs (Roy and von Arnim, 2013). Organellar mRNA translation (chloroplast and mitochondria) and its coordination with cytoplasmic translation is beyond the scope of this chapter; therefore, the reader is referred to recent reviews (Gonzalez and Giegé, 2014; Janska and Kwasniak, 2014; Tiller and Bock, 2014). Here, we detail the process of cytoplasmic translation, its machinery and regulation in plant cells as a drama that occurs in several acts.

DELIVERY OF THE SCRIPT: FROM PRE-mRNA TO QUALITY-CHECKED CYTOSOLIC mRNA

Following the selection of the transcript start site and polymerization of approximately the first 20 nucleotides of the pre-mRNA by RNA polymerase II, the 5′-end of the nascent transcript is modified by the addition of a 5′-m7GpppN-cap structure. This event augments subsequent steps in pre-mRNA biogenesis including intron removal by the spliceosome (Izaurralde et al., 1994) and the cleavage event that marks the 3′-end and site of poly(A) addition (Cooke and Alwine, 1996; Hunt, 2011). Mechanisms of 5′-cap addition in plants are not well studied, but are thought to resemble those of other eukaryotes. The 5′-cap provides protection for the mRNA until it is removed by the decapping machinery and subsequent degradation occurs in a 5′ to 3′ manner (Jiao et al., 2008). As will be discussed, the cap structure also plays a definitive role in the selection of an mRNA for translation. At the 3′ end of the pre-mRNAs, the process of cleavage and polyadenylation has both highly conserved eukaryotic and plant-specific features (Hunt, 2011). The 3′-poly(A) addition site of an individual gene transcript can vary, with ∼25% of Arabidopsis thaliana genes displaying multiple 3′ cleavage sites (Wu et al., 2011). This heterogeneity in the 3′ untranslated region (3′UTR) is likely to impact mRNA stability as well as translation. Also pertinent to translation can be features of the 5′-leader sequence prior to the initiation codon of the protein-encoding open reading frame (ORF), referred to as the 5′ untranslated region (5′UTR) or 5′ leader. Sequences or secondary structures within the 5′UTR can predispose a transcript to distinct translational regulation (Arribere and Gilbert, 2013), as can the presence of short upstream ORFs (uORFs) (Roy and von Arnim, 2013). High-throughput mRNA sequencing (mRNA-seq) has further expanded appreciation for transcript isoform variants that arise due to selection of the site of transcript initiation and variation in intron selection that are regulated in environmental and developmental contexts (Yamamoto et al., 2009). Of these two, variation in intron removal appears to be more prevalent, but both lead to further diversity and potential regulation of protein expression (Filichkin et al., 2010; Li et al., 2010; Reddy et al., 2013).

The mechanism of constitutive intron splicing of plant pre-mRNAs is generally similar to the pathway detailed in yeast and mammals (Reddy, 2007; Koncz et al., 2012; Reddy et al., 2013). An aspect of this process is the recording of splicing events by binding of an exon junction complex (EJC) 20–30 nt upstream of the site of intron removal. There is modulation of intron removal through regulation of the selection of alternative splice sites and intron retention, affecting upwards of 60% of plant mRNAs during development or due to environmental influences (Filichkin et al., 2010; Wu et al., 2011; Filichkin and Mockler, 2012; Kalyna et al., 2012; Marquez et al., 2012; Syed et al., 2012; Leviatan et al., 2013; Staiger and Brown, 2013). Alternative splicing and intron retention events have numerous consequences, ranging from the generation of transcript isoforms that encode distinct proteins or are differentially regulated at the level of message stability, transport, localization or translation. When transcription or splicing produces a transcript containing a premature termination codon, typically upstream of an EJC, the mRNA is targeted for nonsense mediated decay (NMD) after the first round of translation (Reddy et al., 2013). Those transcripts that survive the pioneering round of translation are templates for protein synthesis until they are targeted for degradation or sequestered into translationally inactive complexes and removed from the “cast of actors” in the drama that is translation.

ACT 1: INITIATION OF TRANSLATION

The most well studied aspect of translation in eukaryotes is the initiation phase, which is by far considered currently to be the predominant level of regulation. Initiation of translation of a cytosolic mRNA utilizes both the 5′-m7GpppN-cap and the 3′-poly(A) tail with initiation factors that specifically recognize these features to start the process of initiation of translation. Baker's yeast (Saccharomyces cerevisiae), has provided a genetic treasure trove for structural and functional insight of the highly interactive initiation machinery. Comparative studies have shown that the machinery and their functions are highly conserved, although there are some interesting differences across the spectrum of eukaryotes. In fact, there are remarkable tales of diversity in the machinery that are unique to various organisms and ecological niches (Hernández and Vazquez-Pianzola, 2005; Hernández et al., 2012). Several recent reviews on translation provide mechanistic and structural details of translation derived with S. cerevisiae and mammalian systems (Sonenberg and Hinnebusch, 2009; Jackson et al., 2010; Lorsch and Dever, 2010; Hinnebusch, 2011; Aitken and Lorsch, 2012; Dever and Green, 2012; Hernández et al., 2012; Hershey et al., 2012; Hinnebusch and Lorsch, 2012; Valasek, 2012; Voigts-Hoffmann et al., 2012; Lomakin and Steitz, 2013; Hinnebusch, 2014; Mead et al., 2014; Merrick and Harris, 2014). Translation in plants has been reviewed with different emphases in the past five years (Bailey-Serres et al., 2009; Muench et al., 2012; Muñoz and Castellano, 2012; Echevarría-Zomeño et al., 2013; Browning, 2014; Gallie, 2014), and several historical reviews provide the back story (Browning, 1996; Bailey-Serres, 1999; Kawaguchi and Bailey-Serres, 2002; Browning, 2004; Gallie, 2007). As will be described, the translational machinery of plants resembles that of S. cerevisiae and mammals. Because plants have unique biological activities, such as photosynthesis and the capacity to respond to stresses in situ, they have evolved translational control mechanisms relevant to their needs. This chapter will outline the process of initiation, elongation and termination as largely derived from detailed studies in S. cerevisiae and mammals, but will include specific aspects of the plant apparatus where known. Our knowledge of plant translation is based largely on the Arabidopsis thaliana accession Col-0 (referred to here as Arabidopsis) and the in vitro system derived from the germ (embryo) of hexaploid bread wheat (Triticum aestivum). Undoubtedly there will be myriad differences within the plant kingdom, not only in the translational apparatus but modulation of protein synthesis as is needed in particular ecological niches and environmental circumstances.

THE ACTORS: THE BASIC MACHINERY OF INITIATION

The current estimate of the number of “basic” initiation factors of eukaryotes is >16 and growing (see Table 1). The unified nomenclature for these proteins/complexes includes five categories for the different aspects of the initiation process (Safer, 1989). These are the eukaryotic initiation factors (eIF) 1 to 6. Table 1 includes several additional proteins that are now being considered part of the translational machinery, but have yet to be evaluated in plants, although in many cases a plant ortholog has been recognized. Initiation factor nomenclature is challenging, especially the names of the initiation factors which have evolved within eukaryotic phyla. eIFs include single or multi-subunit protein complexes that are distinguished by complex number (i.e., eIF2, 3, 4) and Roman letters or Greek letters (i.e., eIF2A or eIF2α), each of which is a different complex or protein. Some proteins were originally designated eIFs because of their ability to stimulate rabbit reticulocyte in vitro translation. For example, the eIF2C family turns out to correspond to the Argonautes that participate in RNA-mediated gene silencing (Chen, 2010). Why the addition of an AGO was found to stimulatory is unknown, but AGO1 copurifies with membrane-associated ribosomes during microRNA (miRNA)-mediated translational inhibition in Arabidopsis (Li et al., 2013b).

Table 1 presents the current nomenclature of proteins with known functional activities in mRNA translation in the model plant Arabidopsis thaliana. More than one functional gene encodes most of these factors or factor subunits. Therefore, there are multiple isoforms of each factor or factor subunit, which could accumulate in a distinct quantitative, spatial or temporal manner which may have functional consequence.

A schematic of the initiation process is shown in Figure 1 and emphasizes where plant translation is known to differ from that of yeast or mammals. In the next section we introduce and present details about the initiation factors and their interactions with other actors, mRNA, tRNAs and the ribosome, the prima donna. The order of the description of members of these acting troupes corresponds to the sequence of their appearance on the stage with the 40S ribosomal subunit. The 40S ribosome/associated factors and mRNA/associated factors are then joined by the 60S ribosome to form the functional 80S ribosome complex for elongation of the polypeptide. The 60S subunit possesses the peptidyl transferase activity to join together amino acids as directed by the codon sequence of the mRNA. After the introduction of the initiation factors, we consider the first act of protein synthesis: the sequence of events that culminates in initiation of polypeptide synthesis. The second and third acts, elongation and termination of protein synthesis will introduce several new performers (i.e., eEFs, eIF6, RACK1, ABCE1, and eRFs). There are also two encore events that have garnered attention in recent years that involve efficient recycling of ribosomes for maintained translation of an mRNA or in some cases re-initiation at a downstream open reading frame on an mRNA (von Arnim et al., 2014). There are also side shows of translation including mRNA turnover (see section on “Curtains for some mRNAs”) and protein degradation (for recent reviews in this series see Callis, 2014; Choi et al., 2014).

eIF2 GROUP AND tRNAMET

This group of factors functions in formation of the ternary complex comprised of Met-tRNAi Met ·eIF2·GTP and the exchange of GDP for GTP from eIF2·GDP by eIF2B (also called guanine nucleotide exchange factor or GEF). The eight known proteins of this group have challenging names (Table 1). eIF2A(not to be confused with eIF2a or eIF2Ba) and eIF2D (not to be confused with eIF2Bδ) are new members of the eIF2 group in animals (Komar et al., 2012). The genes appear to be conserved in plants, but their role in plant initiation is not currently known.

Also to be considered along with this group is the initiator Met-tRNAi Met, which has a very specific role in the selection of the correct initiation codon (AUG). This tRNA does not function in elongation and can be distinguished from Met-tRNAMet used for addition of internal methionine residues. Initiator tRNAs have evolved several strategies for this role and avoiding interaction with elongation factor EF1A (reviewed in Kolitz and Lorsch, 2010). Plants and fungi appear to use a strategy of modification of a certain nucleotide in the T-loop with a large O-ribosylphosphate moiety to prevent interaction of initiator Met-tRNAi Met with eEF1A.

eIF2 and Ternary Complex Formation

eIF2 is among the most studied of the translation initiation factors. The primary role of this heterotrimeric complex in both eukaryotes and Archaea is to bring the Met-tRNAi Met and GTP to the ribosome, a task performed by the single polypeptide factor IF2 in eubacteria (reviewed in Schmitt et al., 2010). The eIF2 complex is composed of three subunits, designated eIF2α, eIF2β and eIF2y. eIF2α and eIF2β interact with eIF2y which forms the core of the complex and also contains the GTP nucleotide binding site. This factor has structural similarity to other GTP binding factors such as elongation factors EF-Tu (prokaryotic) or eEF1A (eukaryotic) (Schmitt et al., 2010). A zinc-binding domain is present in eIF2β that is similar to one found in eIF5 and is proposed to play a role during start codon recognition (Nanda et al., 2013). The major binding site of eukaryotic Met-tRNAi Met appears to the eIF2y sub-unit and there is less contribution to binding of Met-tRNAi Met by eIF2α than eIF2β in eukaryotes; whereas in Archaea eIF2α and eIF2β comprise the major binding site of Met-tRNAi Met (Schmitt et al., 2010). eIF2 and associated proteins have been purified from wheat germ and biochemically studied (Benne et al., 1980; Lax et al., 1982; Osterhout et al., 1983; Seal et al., 1983; Shaikhin et al., 1992; Benkowski et al., 1995a, b). Structural and functional similarity of plant eIF2 to yeast and mammalian eIF2 are expected, although there could be plant specific molecular interactions of the subunits or Met-tRNAi Met given that plant eIF2β lacks the third poly-lysine region in the N-terminal domain found in other eukaryotic eIF2β subunits (Metz and Browning, 1997).

Table 1.

Initiation Factors of Arabidopsis

t01a_01.gif

Continued.

t01b_01.gif

Phosphorylation of eIF2

Mammals possess four eIF2 kinases: (HRI, heme-regulated inhibitor; PKR, double stranded RNA-dependent kinase; PERK, PKR-like ER kinase; GCN2, general control non-derepressible-2 kinase). All phosphorylate a conserved serine residue (Ser51) in mammalian eIF2α that inhibits initiation of translation in response to various stresses. eIF2B (see below) cannot easily dissociate from phosphorylated eIF2α and therefore guanine nucleotide exchange is inhibited depleting available eIF2 for ternary complex formation (reviewed in Donnelly et al., 2013). Despite early reports of a “PKR-like” activity in virus-infected plants (Hiddinga et al., 1988; Langland et al., 1995; Langland et al., 1996; Chang et al., 1999), no specific kinase could be purified and the sequence of a putative PKR ortholog is absent from plant genomes (Immanuel et al., 2012). GCN2 is therefore the only recognizable plant eIF2α kinase at this time and targets a similar serine residue in plant eIF2α (Halford et al., 2004; Byrne et al., 2012; Li et al., 2013a; Wang et al., 2014). Other eIF2α kinases may exist, but have yet to be described. GCN2 was identified in yeast in response to nutrient deprivation, particularly amino acid or purine starvation (Hinnebusch, 2005), but it is induced by other stresses (e.g., UV, osmotic and oxidative stress) and functions similarly in mammals (Donnelly et al., 2013). The general amino acid control pathway in yeast is controlled by the transcription factor GCN4 which activates transcription of numerous genes in many biosynthetic pathways in response to nutrient deprivation (Hinnebusch, 2005). The translation of yeast GCN4 mRNA, utilizes four short upstream open reading frames (uORFs) in the 5′ leader sequence to control expression of the ORF encoding GCN4.

GCN2 kinase, which is activated during nutrient deprivation by sensing tRNAs that are unchanged (i.e., low amino acid levels), phosphorylates eIF2α, preventing its interaction with eIF2B for guanine nucleotide recycling. The amount of available ternary complex falls and protein synthesis initiation is inhibited. When the levels of ternary complex are high, initiation occurs at the first AUG in the 5′ leader and elongation and termination precede; subsequent reinitiation events are likely at uORFs 2–4 and therefore initiation at the AUG of the GCN4 coding region is limited. However, when ternary complex is low, reinitiation at uORFs 2–4 is less likely and the 40S ribosomes continue to scan, acquire ternary complex, reach the AUG of the GCN4 ORF and commence synthesis of GCN4 (Hinnebusch, 2005). The process also involves the transient maintenance of eIF3 association with the ribosome as it translates the first of the four uORFs under starvation conditions (Szamecz et al., 2008). This is an exquisitely complex regulatory system in yeast for sensing and response to nutrient status through translational control.

Figure 1.

Overview of the steps of translation initiation in the cytoplasm of plants.

Once the mRNA has been exported from the nucleus into the cytoplasm it interacts with a cap-binding complex (eIF4F or plant-specific eIFiso4F) at the 5′ end and PABP at the 3′ end. Additional factors, eIF4A and eIF4B are recruited to the mRNA to promote ATP-dependent unwinding of secondary structure prior to interaction with the 43S PIC (pre-initiation complex). The 43S PIC is formed from the 40S ribosome and its associated factors eIF1, eIF1A, eIF3 and eIF5. eIF1, eIF1A, eIF3 and eIF5 form the multi-factor complex (MFC), although it is not clear if this assembles prior to interaction with the ribosome or on the ribosome. Addition of ternary complex (TC) of eIF2·Met-tRNAi·GTP completes the preparation of the PIC. This then engages the mRNA and its associated factors (eIF4F/eIFiso4F, eIF4A, eIF4B, PABP) to form the 48S scanning complex (open conformation), which functions to scan the 5′ untranslated region of the mRNA in the 5′ to 3′ direction in order to select the AUG (i.e., A/GXXA+1UGG). Once the AUG is selected the 48S complex switches to the closed conformation securing the Met-tRNA, in the P-site and ejecting eIF1. eIF5B·GTP binds to the 48S ribosome complex and the process for joining with the 60S subunit commences, and eIFs 6, 5, 3, and 2 exit the 48S ribosome. Completion of joining of the 60S ribosome results in the hydrolysis of eIF5B·GTP and its release along with eIF1A. The now functional 80S ribosome may now start peptide elongation (see Figure 2). The role of eIF2B in guanine nucleotide recycling of eIF2 in plants is unclear at this time (shown with a green line). Note that the factors and ribosomal subunits are not to scale.

f01_01.tif

Arabidopsis GCN2 kinase complements yeast GCN2 kinase suggesting some aspects of the yeast general amino acid control (GAAC) mechanisms may be conserved in plants (Zhang et al., 2003). Herbicides (i.e., chlorosulfuron, glyphosate) that inhibit amino acid synthesis and thus induce amino acid starvation result in induction of GCN2 and phosphorylation of eIF2α (Zhang et al., 2008b). GCN2 also functions in response to purine starvation, UV irradiation, wounding, hormones, cold shock (Lageix et al., 2008), cadmium stress (Sormani et al., 2011b), amino acid metabolism and sulfur signaling (Byrne et al., 2012), but evidently not virus infection (Zhang et al., 2008b). The phosphorylation of eIF2α in response to purine starvation was correlated with reduced large polysome complexes, suggesting that it can generally inhibit initiation (Lageix et al., 2008; Sormani et al., 2011b). To date, there is no direct evidence that GCN2 regulates ternary complex formation in plants or plays a role in translation of mRNAs with uORFs.

eIF2α and eIF2β subunits were reported to be targets of CK2 (formerly casein kinase II) in vitro, but the role of phosphorylation of these subunits in vivo is not known (Dennis and Browning, 2009; Dennis et al., 2009). Interestingly, none of the subunits of eIF2 were reported to be phosphorylated in a study of the effects of light/dark on the phosphoproteome of the translational apparatus (Boex-Fontvieille et al., 2013). There is still much to learn about the control of protein synthesis in plants in response to various types of stresses and to what level eIF2 subunit phosphorylation regulates the process.

In plants, “eIF2B or, not 2B, that is the question”

As described above, one of the major mechanisms used by yeast and particularly mammals for the regulation of initiation of translation is the phosphorylation of a single conserved serine residue on eIF2α. This phosphorylation event prevents eIF2B from dissociating from eIF2 during recycling of GDP for GTP, prohibiting the formation of a new ternary complex. This inability to recycle GDP/GTP effectively shuts down initiation in the absence of ternary complex formation (reviewed in Donnelly et al., 2013).

An eIF2B-like activity has not been purified from a plant source, although genes with similarity to mammalian eIF2B subunits are encoded by Arabidopsis (see Table 1) and phosphopeptides have been reported for the eIF2By and eIF2Bδ subunits (Boex-Fontvieille et al., 2013), suggesting that the proteins are expressed and modified.

Evidence that eIF2B recycling may not be necessary, and thus phosphorylation of eIF2α may not have as strong an inhibitory effect on translation, is the report that binding of GDP to eIF2 is only about 10-fold higher than that of GTP in comparison to the ∼100-fold difference for mammalian eIF2 (Shaikhin et al., 1992). Thus the requirement for eIF2B recycling may be less in plants allowing for continued translation even in the presence of eIF2a phosphorylation. There is a need for further studies to corroborate biochemically what is known about plant GCN2 kinase, its role in eIF2α phosphorylation and eIF2B (i.e. if it exists as a complex) activity in GDP recycling and global translational activity. It will also be intriguing to decipher the cross-talk that occurs between pathways that activate GCN2 and the Target of Rapamycin (TOR) pathway, which is likely involved in sensing sucrose and other nutrients in plants and regulating translation of certain mRNAs (Immanuel et al., 2012; Robaglia et al., 2012).

eIF3 Group

The sole performer of this group, eIF3, is a complex of six subunits (a, b, c, l, g, j) in yeast, but 13 subunits (a-m) in higher eukaryotes including plants (Browning et al., 2001). The principal role of eIF3 is to bind to the 40S subunit to participate in the formation of the 43S pre-initiation complex (PIC) comprised of the 40S subunit, and the ternary complex (eIF2·GTP·tRNAMet), along with the factors eIF1, eIF5 and eIF1A. eIF3 acts as a bridge to facilitate binding of mRNA with its associated factors, eIF4F, eIF4A, eIF4B and Poly(A) binding protein (PABP), with the PIC, forming a 48S scanning complex. Recent cryo-EM and structural data for eIF3 suggest that it “hugs” the 40S ribosome with contacts that span the mRNA entry and exit sites (Hashem et al., 2013; Liu et al., 2014).

eIF3

The eIF3 complex shares “architectural” similarities to other large complexes, the 26S proteasome lid and the COP9/signalosome that are collectively known as PCI complexes (Pick et al., 2009). The eight proteins that form the octamer core of each of these complexes share motifs known as PCI and MPN domains. The characteristic composition of these PCI complexes are six subunits with PCI domains and two with MPN domains (Pick et al., 2009). Higher eukaryotic eIF3 subunits a, c, e, and I all have PCI domains, k and m have structurally related winged helix domains (Zhou et al., 2005), and f and h have MPN domains. The PCI/MPN containing subunits form the “octamer” core that is similar to that found in the proteasome lid (Querol-Audi et al., 2013). The remaining subunits, b, d and g have RNA Recognition Motif (RRM) domains (Cuchalova et al., 2010); subunits b and i have WD40 domains and eIF3g has a zinc-binding domain (Hinnebusch and Lorsch, 2012; Valasek, 2012; Voigts-Hoffmann et al., 2012; Hashem et al., 2013; Querol-Audi et al., 2013). Recent cryo-EM reconstructions of mammalian eIF3 and the 43S PIC indicate that eIF3 has five lobes and the PCI/MPN octamer forms the functional core of eIF3 (Siridechadilok et al., 2005; Khoshnevis et al., 2012; Hashem et al., 2013; Querol-Audi et al., 2013). The placement of the eIF3 subunits and their contacts with the ribosome and other initiation factors awaits further structural data, but a picture is beginning to emerge at the molecular level (Wilson and Doudna Cate, 2012; Hashem et al., 2013; Liu et al., 2014). Yeast eIF3 is also implicated in termination of protein synthesis, termination codon read-through and ribosome reinitiaton suggesting that we still have much to learn about this multi-functional factor and its roles during translation in all organisms (Pisarev et al., 2007; Beznosková et al., 2013).

Plant eIF3 (wheat and Arabidopsis) has been purified and its biochemical analysis suggests strong similarity both in number of subunits and sequence to mammalian eIF3 (Checkley et al., 1981; Lauer et al., 1985; Heufler et al., 1988; Burks et al., 2001). Subunits eIF3m and eIF3l were first described in plant eIF3 (Burks et al., 2001) and subsequently identified in mammalian eIF3. Biochemical and yeast-two hybrid analysis have implicated some of the Arabidopsis eIF3 subunits in association with the 26S proteasome and COP9 signalosome complexes or subunits (Karniol et al., 1998; Yahalom et al., 2001; Kim et al., 2004; Paz-Aviram et al., 2008). Both the 26S proteasome and COP9 signalosome play roles in protein turnover. These interactions with eIF3 or its subunits suggest that there may be additional unknown functions for some of the eIF3 subunits or some sort of communication between these large PCI complexes to coordinate various aspects of the cellular dramas of translation and protein degradation (Kim et al., 2001; von Arnim and Chamovitz, 2003).

eIF3 plays a pivotal role in initiation of translation via its interactions with numerous factors as well as the ribosome. It is therefore not surprising that only few Arabidopsis eIF3 subunit mutants have been reported. Five of the subunits for eIF3 (see Table 1) are encoded by a single gene in Arabidopsis (a, e, f, h, k) and eight are encoded by two genes (b, c, d, g, i, j, l, m). Mutations in the single genes for eIF3e or eIF3f cause male gametophytic lethality (Yahalom et al., 2008; Xia et al., 2010). Genotypes that only express eIF3f in pollen indicated that the absence of eIF3f is also embryo lethal (Xia et al., 2010). Partial loss of function alleles of the single eIF3h gene are viable but display multiple developmental defects, including reduced male gamete transmission. Interestingly, eIF3k appears to be non-essential under normal growth conditions (Tiruneh et al., 2013).

eIF3 and initiation/reinitiation

Several eIF3 subunits are implicated in translation of mRNAs with unusual 5′ leader sequences. These include viral mRNAs and plant transcripts with that have one or more uORF upstream or overlapping with the main protein coding ORF (mORF) (See also, Reinitiation involving uORFs section).

Early insight into the nuanced roles of Arabidopsis eIF3 subunits came from the discovery of its function in the initiation of the 35S cauliflower mosaic virus (CaMV) mRNAs during infection. The 5′ leader of this viral mRNA is long, highly structured and contains several short ORFs. A viral encoded protein called TAV (transactivation/viroplasmin) interacts with eIF3 through eIF3g to retain eIF3 on ribosomes and promote reinitiation at the initiation codon of the first long viral ORF (Park et al., 2001; Park et al., 2004). Another initiation factor, eIF4B is also involved in the TAV-mediated reinitiation process (see below). A host protein called RISP (reinitiation supporting protein) was described that supports reinitiation during CaMV infection and interacts with eIF3 through the eIF3a and eIF3c subunits (Thiebeauld et al., 2009). TAV binding to the TOR kinase was shown to be critical for the reinitiation event (Schepetilnikov et al., 2011). This suggests that el F3 can be essential in reinitiation, in a manner exploited by CaMV and possibly other viruses and connects translation to the TOR signaling pathway in plants.

eIF3 is also important in translation of endogenous plant mRNAs that possess a uORF. Remarkably, over 30% of the protein coding mRNAs of Arabidopsis possess a 5′ leader with one or more uORF. Of these, ∼1% encode a peptide that is evolutionary conserved among angiosperms (CPuORFs) (Jorgensen and Dorantes-Acosta, 2012). The presence of a uORF generally reduces the level of translation of the mORF, due to efficient initiation of translation of the uORF and limited initiation at the mORF. DNA microarray analysis of mRNA present on polysomes isolated from eIF3h mutants suggested that eIF3h is necessary for reinitiation on mRNAs with uORFs (Kim et al., 2004; Kim et al., 2007; Roy et al., 2010; Zhou et al., 2010a; Zhou et al., 2014a). Numerous studies document uORFs that regulate mORF translation in plants, including several that exert their regulation based on metabolite availability (Roy and von Arnim, 2013). uORF-containing mRNAs of Arabidopsis include those encoding the S class of bZIP transcription factors and Auxin Response Factors (ARFs) (Kim et al., 2004; Nishimura et al., 2005; Rahmani et al., 2009). Both eIF3h and the 60S ribosomal protein RPL24 are required for efficient reinitiation of translation of the AtbZIP11 (ATB2) and ARF mORF (Kim et al., 2004; Nishimura et al., 2005; Kim et al., 2007; Roy et al., 2010; Zhou et al., 2010a; Zhou et al., 2014a), although global analyses of polysomal RNA do not strongly support a role of RPL24 in this process (Tiruneh et al., 2013).

The reinitiation downstream of the uORFs of ARF3 mRNA is mediated by auxin as well as TOR kinase (Schepetilnikov et al., 2013). Auxin triggers TOR activation, followed by its association with polysomes, where it phosphorylates ribosomal protein S6 kinase (i.e., AtS6K1) rendering it active to phosphorylate eIF3h, evidently after dissociation from the ribosome. This discovery makes a direct link to auxin-mediated signaling through plant TOR/S6K1 and the translational apparatus needed to reinitiate translation of ARF mRNAs possessing uORFs and provides unequivocal evidence that TOR contributes to gene-specific translational control in plants (Schepetilnikov et al., 2013).

Functional characteristics of other eIF3 subunits are emerging. The overexpression of eIF3g in wheat appears to enhance tolerance to drought and other abiotic stresses (Singh et al., 2007; Singh et al., 2013). Interestingly, the only monoclonal antibody to wheat eIF3 subunits that showed any inhibitory activity in vitro was to eIF3g and it inhibited mRNA binding to 40S ribosomes in vitro (Lauer et al., 1985; Heufler et al., 1988). This observation suggests that eIF3g facilitates mRNA binding to 40S ribosomes. Further, eIF3g was shown to be involved in reinitiation events required to translate GCN4 mRNA in yeast (Cuchalova et al., 2010) and in the reinitiation of CaMV in plants (Park et al., 2001; Park et al., 2004). It can be speculated that eIF3g has a role(s) in reinitiation events through direct interaction with the mRNA and ribosome, but more work will be needed to further establish the function(s) of the eIF3g and other eIF3 subunits during initiation and reinitiation events.

Many observations suggest that there is “cross-talk” between the PCI/MPN complexes in the ribosome-mediated synthesis and proteasome-mediated degradation of proteins. Since these complexes share structural similarity in many of their subunits (Pick et al., 2009), it will be illuminating to figure out the structural and regulatory role of these subunits/complexes and their interactions, from their opening acts in synthesis to the “death scene” in degradation of proteins.

Regulation of eIF3 through Phosphorylation

Several subunits of eIF3 are reportedly phosphorylated by highly specific kinases. As mentioned, this includes TOR-regulated phosphorylation of eIF3h by AtS6K1 (Schepetilnikov et al., 2013). eIF3i was identified as a target of brassinosteroid insensitive receptor kinase (BRI1) and was shown to co-immunoprecipitate with BRI1 (Jiang and Clouse, 2001; Ehsan et al., 2005). This suggests a connection between brassinosteroid signaling and eIF3 function, although the effect of the phosphorylation of eIF3i on eIF3 function is not yet known. The brassinosteroid signaling pathway has been proposed to have similarities to TGF-β signaling in mammals. The TGF-β kinase targets the eIF3i subunit, suggesting that there may be conserved signaling pathways and regulation between plants and animals, albeit repurposed in the individual phyla.

Additional pleiotropic kinases such as CK2 (Mulekar and Huq, 2013) have been shown to be active against several plant initiation factors (eIF2α, eIF2β, eIF5) in vitro, including multiple phosphorylation sites in eIF3c (Dennis and Browning, 2009). An in vivo phosphoproteome study of the light/dark response identified multiple subunits of AteIF3 (b, c, d) as phosphorylation targets (Boex-Fontvieille et al., 2013), including eIF3c sites that are comparable to those identified as CK2 substrates in wheat (Dennis and Browning, 2009).

Clearly there is complicated regulation of translation through multiple eIF3 subunit phosphorylation events and it will be necessary to identify the various kinases and their roles in eIF3 phosphorylation regulation at the molecular level in plants and how it compares with regulation in other organisms.

eIF4 Group

This group of factors interacts with the mRNAand facilitates its binding to the 43S PIC (Jackson et al., 2010; Valasek, 2012; Hinnebusch, 2014). Within this group are the cap-binding complexes, including eIF4F (all eukaryotes) and eIFiso4F (plant-specific). The individual subunits of these complexes are designated as the cap-binding proteins, eIF4E or eIFiso4E, and the large scaffolding proteins, eIF4G or eIFiso4G. Other members of this group are eIF4A, a DEAD box RNA helicase and eIF4B, a RNA binding protein. Both eIF4A and eIF4B are single polypeptides and interact with the large subunits of eIF4F and eIFiso4F. Another member of this group is eIF4H in mammals; however, a comparable factor has not been identified in yeast or plants. Although PABP is not an official member of this group, it will be considered here as it binds to the poly(A) tail of mRNA and interacts with other eIF4 group members during binding of the mRNA to the ribosome. Additional RNA helicases have been identified as having roles in initiation such as yeast DED1 or mammalian DHX29. These have not yet been formally designated as “eIFs” but eventually may be added to the “cast of characters” (Jackson et al., 2010). Plants have comparable RNA helicases (Bush et al., 2009), but their role in plant translation has not been elucidated and they may also have other specific roles in post-transcriptional processes. For example, the nuclear-localized AteIF4AIII was shown to function in nuclear pre-mRNA/mRNA movement during hypoxia (Koroleva et al., 2009a; Koroleva et al., 2009b) and the DEAD box helicase AtRH57 appears to be involved in rRNA processing in response to glucose and abscisic acid (Hsu et al., 2013).

eIF4A

This was the first RNA helicase to be identified and has been called “the godfather of helicases” (Rogers et al., 2002). A number of reviews on eIF4A and the DEAD/DEAH family of helicases summarize its role in the initiation of translation in mammalian and yeast systems (Webster et al., 1991; Parsyan et al., 2011; Andreou and Klostermeier, 2013; Linder and Fuller-Pace, 2013; Marintchev, 2013; Putnam and Jankowsky, 2013). Despite being the founding member of the DEAD box helicases, so named for a conserved amino acid motif (DEAD), eIF4A is the “outlier” in the family. It possesses a minimal helicase core but lacks additional accessory domains found in other helicases (Andreou and Klostermeier, 2013, 2014). eIF4As are highly conserved proteins, and based on sequence similarity plant eIF4A is likely to share structural and mechanistic details with eIF4A from yeast or mammals.

eIF4A is a non-processive bi-directional RNA dependent ATPase that functions locally to unwind short duplexes and lacks any specificity for RNA sequence (Marintchev, 2013). It has two RecA domains that in the presence of RNA and ATP come together to form the “closed” catalytically active conformation in a dumbbell-like shape (Meng et al., 2014). eIF4G and eIF4B binding to eIF4A favors the closed conformation and likely stimulates Pi release and/or nucleotide exchange from eIF4A (see eIF4G below, reviewed in Marintchev, 2013). It is thought that eIF4A complexed with eIF4G and eIF4B interacts with the 5′ end of the mRNA to relax secondary structure in an ATP-dependent manner in preparation for the binding of the 43S PIC. eIF4A further functions to remove secondary structures and/or RNA binding proteins during the scanning of the 5′ leader by the PIC (Parsyan et al., 2011; Marintchev, 2013; Andreou and Klostermeier, 2014).

Biochemical studies of wheat eIF4A suggest that it is similar to mammalian and yeast eIF4A (Lax et al., 1986; Abramson et al., 1988; Balasta et al., 1993; Bi et al., 2000). Studies of Arabidopsis eIF4A during the cell cycle led to the suggestion that proliferating cells display high canonical eIF4A association with the cap binding complex whereas quiescent cells may have other types of RNA helicases associated with the cap-binding complexes (Bush et al., 2009). Overexpression of pea (Pisum sativum) eIF4A (PDH45) resulted in increased resistance to salt stress in rice (Oryza sativa) and tobacco (Nicotiana tobaccum), suggesting a role in stress responses (Tajrishi et al., 2011; Sahoo et al., 2012). A T-DNA insertion in one of the two eIF4A gene paralogs of Brachypodium distachyon resulted in a slow-growing, dwarf phenotype that could be partly reversed by heterologous expression of Arabidopsis eIF4A-1 (Vain, et al, 2011). This phenotype is similar to a T-DNA insertion mutant in Arabidopsis eIF4A-1 (Vain et al., 2011), one of the three genes encoding this protein (Table 1).

Phosphorylation of eIF4A

There is proteomic evidence that cytoplasmic eIF4A1/2 of Arabidopsis associates with the cyclin dependent kinase CDKA; however, an effect on eIF4A function by CDKA has not been demonstrated (Hutchins et al., 2004). eIF4A is rapidly phosphorylated in response to hypoxia in maize (Zea mays), but the relevant kinase or sites were not identified (Webster et al., 1991). Wheat eIF4A was also shown to be phosphorylated at an apparent single site in response to heat shock (Gallie et al., 1997). The recent phosphoproteomic analysis of the light/dark transition shows that AteIF4A1, 2 and 3 gene products are phosphorylated (Boex-Fontvieille et al., 2013).

eIF4B

This is the only initiation factor that lacks a high degree of sequence similarity between yeast, mammals and plants. It is largely accepted that eIF4B functions as a RNA binding protein and enhances the helicase activity of eIF4A, presumptively by augmenting both ATP and RNA binding (Hinnebusch and Lorsch, 2012). In yeast, eIF4B binds eIF4G and induces a conformational change that in turn promotes the binding of eIF4A and increases its RNA helicase activity (Park et al., 2012). Yeast eIF4B has also been shown to bind to the 40S ribosomal protein RPS20 near the mRNA entry site, which may facilitate interaction of eIF4A (Walker et al., 2012; Zhou et al., 2014b) and recent data suggest a mechanism in yeast for eIF4B to promote association of eIF4A with eIF4F (Park et al., 2012). eIF4B is not an essential gene in yeast, but its deletion produces a cold sensitive phenotype (Altmann et al., 1993).

Extensive biochemical and kinetic characterization of the interactions of wheat eIF4B, eIF4A, eIF4G/eIFiso4G and PABP confirm that the interactions are similar to other organisms (reviewed in Gallie, 2014; Le et al., 1997; Bi and Goss, 2000; Bi et al., 2000; Khan and Goss, 2005; Cheng and Gallie, 2006, 2007; Cheng et al., 2008; Khan et al., 2008; Khan et al., 2009; Mayberry et al., 2009; Cheng and Gallie, 2010; Yumak et al., 2010; Khan and Goss, 2012; Cheng and Gallie, 2013). Wheat eIF4B has two tandem domains for interaction with eIF4A and PABP separated by a RNA binding domain in addition to binding domains for eIF4G/iso4G and eIF3g. These tandem binding domains are the most highly conserved parts of plant eIF4B. This suggests that eIF4B may interact with more than one molecule of eIF4A or PABP at a time during initiation events. Further, the interactions with eIF4G/iso4G and eIF4A appear to be specific to plant eIF4B, suggesting divergent evolution of this factor from other eukaryotes (Gallie, 2014).

eIF4B also assists eIF3 in CaMV infection and the TAV-mediated reinitiation on the 35S transcript. Specifically, eIF4B interacts with eIF3g to form a stable 43S PIC in plant cells. Upon binding of the 60S ribosomal subunit at the final step of initiation, eIF4B and eIF3 are released and therefore not found in polysomes of cells not infected by CaMV. However, TAV keeps eIF3 associated with the ribosome, as eIF3 is found in polysomes of infected cells (Park et al., 2004). The overexpression of eIF4B prevents association of TAV with translating ribosomes by competing with TAV for binding to eIF3g (Park et al., 2004). These exploitations of the translation system by a virus suggest that the role of eIF4B may not be solely in stimulation of the helicase activity of eIF4A and eIF4F on mRNA.

Arabidopsis has two forms of eIF4B (eIF4B1 and eIF4B2), which similarly support in vitro translation (Mayberry et al., 2009). Interestingly, a heterozygous Arabidopsis T-DNA activation tagging line that showed necrotic lesions symptomatic of programmed cell death overexpresses eIF4B2 and lines homozygous for a disruption of this gene were embryo lethal (Gaussand et al., 2011). Ectopic overexpression of eIF4B2 recapitulated the necrotic phenotype, leading to the conclusion that too much eIF4B can cause disruptions in gene expression that trigger programmed cell death. These data suggest a fundamental role for eIF4B in the process of initiation in plants (Gaussand et al., 2011).

Phosphorylation of eIF4B

Plant eIF4B is a target of phosphorylation by CK2 and possibly additional kinases (Gallie et al., 1997; Dennis and Browning, 2009). Arabidopsis eIF4B isoforms show differential responses to the isoforms of CK2 (Dennis and Browning, 2009) suggesting that eIF4B activity could potentially be modulated by distinct CK2s. Support for eIF4B phosphorylation was found in the light to dark phosphoproteome (Boex-Fontvieille et al., 2013) and wheat eIF4B was shown to respond to heat shock by dephosphorylation at multiple sites (Gallie et al., 1997). The effect of phosphorylation of plant eIF4B on its various activities needs further study in light of the recent work showing that phosphorylation of mammalian eIF4B and eIF4G influence the formation of an eIF4F/eIF4A/eIF4B complex and stimulate interaction with eIF3 and the 43S PIC (Dobrikov et al., 2012).

The divergence in eIF4B protein sequences between kingdoms suggest that there may be wide latitude in evolutionary constraints and unique mechanisms for regulation for this factor by phosphorylation (Hernández et al., 2010) leaving much to explore for the role of this “nonconserved” factor.

eIF4F and eIFiso4F

The role of eIF4F is to bind to the “cap” on the 5′ end of the mRNA. This is a guanine residue methylated in the 7 position and attached to the first residue of the mRNA through a 5′ to 5′ linkage (m7GpppX). This reverse linkage helps to protect the mRNA, as the decapping of mRNA is one of the first enzymatically-driven steps in a major mRNA degradation pathway (Li and Kiledjian, 2010; Milac et al., 2014) and likely plays roles in plant gene expression during stress and other developmental pathways (Zhang et al., 2013). The m7G structure is recognized by the cap-binding protein eIF4E. eIF4E binds to the scaffold protein eIF4G to form the two-subunit complex called eIF4F, which is conserved in higher eukaryotes. eIF4G helps to assemble eIF4A, eIF4B and PABP on the mRNA to prepare it for binding to the 43S PIC (via interaction of eIF3 with eIF4G and eIF4B), in prepararion for scanning of the 5′ leader for an initiation codon (see below).

One distinction between the plant translational apparatus and that of other eukaryotes is the presence of a second cap-binding protein complex that differs from the canonical eIF4F. This two-protein complex, eIFiso4F, is comprised of eIFiso4G and eIFiso4E (Allen et al., 1992; van Heerden and Browning, 1994; Patrick and Browning, 2012). The cap binding proteins, eIF4E and eIFiso4E, have ∼50% amino acid sequence similarity and form distinct and specific complexes with their respective binding partners, eIF4G and eIFiso4G (Mayberry et al., 2011). However, in the absence of the correct binding partner, mixed complexes will form that function in translation in vitro (Mayberry et al., 2011).

The larger scaffold subunits (eIF4G and eIFiso4G) share similarity in the C-terminal half with the eIF4E binding site and two HEAT (Huntington, elongation factor 3, protein phosphatase 2A, and the yeast TOR1 kinase) domains; however, the N-terminal half of eIF4G is absent in eIFiso4G (Patrick and Browning, 2012). eIFiso4F appears to be necessary for proper growth and development of Arabidopsis, as deletion of both eIFiso4G genes results in slow and stunted growth, pale green rosettes and significant reproductive defects (Lellis et al., 2010). Based on phylogenetic analyses, eIFiso4G appeared in basal plant lineages before eIFiso4E and most likely formed a complex with eIF4E, whereas eIFiso4E emerged around the time flowering plants evolved (Patrick and Browning, 2012).

The role of the eIF4 factors is to bind the mRNA and prepare it for association with the 43S PIC. The current model for this process has the 5′ cap binding to eIF4F through the eIF4E subunit. eIF4G (or eIFiso4G) serves as the scaffold for assembly of eIF4A, eIF4B and PABP (presumably binding the poly(A) tail and circularizing the mRNA at some time) as well as an interaction site for eIF3 (Jackson et al., 2010; Hinnebusch and Lorsch, 2012; Valasek, 2012). Although a structure for an eIF4F complex has not been determined, there are structures for portions of eIF4G in complex with eIF4E or eIF4A and considerable domain mapping for eIF4G from several organisms (Marintchev and Wagner, 2005; Marintchev et al., 2009; Dobrikov et al., 2012; Park et al., 2012), including plant eIF4G and eIFiso4G (Cheng and Gallie, 2010; Cheng and Gallie, 2013).

eIF4G and eIFiso4G

eIF4Gs have one to three HEAT domains depending upon the organism: yeast has one, plants have two, and mammals have three suggesting considerable evolution of the machinery (Hernández and Vazquez-Pianzola, 2005; Hernández et al., 2010; Hernández et al., 2012). HEAT domains are comprised of a series of alpha helices that form a coiled solenoid-like structure and provide surfaces for interaction with proteins and mRNA (Marintchev and Wagner, 2005; Valasek, 2012). Among these interactions are binding to eIF4A, eIF4B, eIF3 and PABP, which all function to bring the mRNA to the 40S subunit to initiate the scanning process (Hinnebusch and Lorsch, 2012).

The two eIF4A Rec A (N-terminal, C-terminal) domains interact with the middle section of the yeast HEAT domain or with the HEAT-1 and HEAT-2 domains of mammalian eIF4G (Marintchev et al., 2009; Hilbert et al., 2011). eIF4G promotes the transition from an “open” to a “closed” form of eIF4A based on crystal structures (Schütz et al., 2008; Marintchev et al., 2009). The model in yeast has been further refined by monitoring conformational changes in solution to include a “half-closed” intermediate for eIF4A that is stabilized upon binding of eIF4G (Hilbert et al., 2011). The closed state conformation of eIF4A is stimulated by ATP and RNA binding. It is also proposed that the closed form has a groove between the two interfaces of eIF4Aand eIF4G that make the nucleotide binding site of eIF4A more accessible to ATP (Hilbert et al., 2011). The oscillations between the half-closed and closed forms may drive the release of ADP/P, and rebinding of ATP to maintain mRNA binding affinity during scanning (Hilbert et al., 2011).

Plant eIFiso4G and eIF4G domains have been mapped and shown to have similar types of interactions with eIF4A, eIF4B and PAPB, but have some differences from the mammalian or yeast interactions (Gallie, 2014). Further structural details will be required to understand how similar or different these plant factor interactions are to other eukaryotes.

An alternative to the current “script” of mRNA binding and unwinding by associated factors prior to binding to the 43S PIC, is that the eIF4 factors assemble on the 43S PIC and then recruit and unwind the mRNA, feeding it directly into the scanning complex (Hinnebusch and Lorsch, 2012). This model has many elements that explain some of the biochemical data but will require further testing not only in yeast but also in mammals and plants to determine if this is an accurate depiction of the scene within the cell.

“4F or, not 4F, that is the question”

The presence of two eIF4F complexes in plants raises the question of whether they have distinct biological activities. eIF4F promotes translation of reporter mRNAs with more secondary structure better than eIFiso4F in a cell-free translation system derived from wheat germ (Gallie and Browning, 2001). In addition, cellular mRNAs were shown to have varying levels of dependence upon eIF4F or eIFiso4F, as well as eIF4B, for optimal translation (Mayberry et al., 2009). These results suggest that plant eIFiso4F and eIF4F may have evolved selective abilities to promote or otherwise regulate translation of specific mRNA populations. What advantage distinct eIF4Fs provide to plants is not yet clear, but they may have pleiotropic roles in the synthesis of proteins involved in plant-specific functions, such as photosynthesis, cellulose biosynthesis, etc.. eIFiso4F was implicated in the specific regulation of translation of an enzyme involved in the synthesis of chlorophyll (Chen et al., 2014) which fits with the observed pale green phenotype of Arabidopsis plants lacking eIFiso4G (Lellis et al., 2010).

Ultimately, structures of plant eIF4F or eIFiso4F in association with the 43S PIC will be needed to determine if there are functional differences in assembly of the initiation complexes in plants as compared to yeast and mammalian systems.

The cast of cap-binding proteins: eIF4E, eIFiso4E and 4EHP

All higher plants have three forms of the cap-binding proteins, eIF4E, eIFiso4E (plant-specific) and 4EHP (4E homologous protein) which all bind to m7GTP-Sepharose (Ruud et al., 1998; Patrick et al., 2014; Kropiwnicka et al., 2015). eIF4E and eIFiso4E are both class 1 cap-binding proteins (Joshi et al., 2005) and form the eIF4F and eIFiso4F complexes with their respective subunits, eIF4G and eIFiso4G (Mayberry et al., 2011; Patrick and Browning, 2012). 4EHP is termed a class 2 cap-binding protein (Joshi et al., 2005) and does not appear to function in canonical translation but has been implicated in regulatory roles for mRNAs during animal development in association with proteins that are not considered part of the canonical translational apparatus (Rom et al., 1998; Rhoads, 2009; Morita et al., 2012). The role of plant 4EHP (previously termed nCBP in plants for “novel” cap-binding protein) is unknown, although it has shown modest ability to stimulate translation with wheat eIFiso4G and appears to bind m7GTP more tightly than other cap-binding proteins (Ruud et al., 1998). There is more to learn about this unusual cap-binding protein and its role(s) in various cellular processes as capped non-coding and small RNAs are discovered and their functions elucidated.

It is also worth mentioning that there is a nuclear cap-binding protein complex (CBP20/CBP80) that shares structural and ancestral similarity to the eIF4E/eIFiso4E cap-binding proteins (CBP20) and eIF4G/eIFiso4G large subunits (CBP80). This complex does not function directly in translation but is important in pre-mRNA splicing, miRNA processing and export of mRNA in plants (Hugouvieux et al., 2001; Papp et al., 2004; Marintchev and Wagner, 2005; Topisirovic et al., 2011; Rogers and Chen, 2013; Gonatopoulos-Pournatzis and Cowling, 2014). There are many unanswered questions about the timing and location of exchange of CPB20 and eIF4E/eIFiso4E from the cap of mRNAs as it transitions from the nucleus to the cytoplasm.

The canonical type 1 plant cap-binding proteins, eIF4E and eIFiso4E, form tight complexes with their respective eIF4G subunits at the nanomolar to sub-nanomolar level (Mayberry et al., 2011). It is unlikely that these complexes readily dissociate given the tight binding affinity. They also do not appear to be regulated by any of the pathways associated with mammalian eIF4E that require dissociation/reassociation (see 4E Binding Proteins below). The crystal structure of wheat eIF4E shows similarities to both mammalian and yeast eIF4E, but revealed an intermolecular disulfide bridge between two plant-specific cysteine residues (Cys-113 and Cys151) that form under oxidizing conditions (Monzingo et al., 2007). This leads to the hypothesis that eIF4E could function as a redox sensor at the level of translational initiation. A constitutively reduced mutant (C113S) and oxidized forms of eIF4E bound m7GTP with a modest 1.5× difference in koff values in NMR (nuclear magnetic resonance) solution studies (Monzingo et al., 2007). Further studies using mass spectrometry and a lysine-specific chemical probe indicated structural changes occurred upon altering the redox state and support the hypothesis of a redox sensor or switch for eIF4E (O'Brien et al., 2013). It remains a tantalizing possibility that the oxidation state of eIF4E (and/or eIFiso4E) may modulate cap binding in a redox-sensing manner in plants during retrograde signaling from the chloroplast to nucleus or other processes that could regulate the level of translation in response to the redox state of the cell.

Arabidopsis thaliana has three genes for the class 1 eIF4E (eIF4E, eIF4E1b, eIF4E1c) and one gene for eIFiso4E (Patrick and Browning, 2012; Patrick et al., 2014). eIF4E is the most highly expressed; the other two eIF4E genes (eIF4E1b, eIF4E1c) correspond to a tandem duplication event within the Brassicaceae with evidence that only eIF4E1b generates a transcript (Patrick and Browning, 2012) (see Table 1 for accession numbers). A number of forms of eIF4E have evolved in other organisms with special functions such as recognition of tri-methylated caps or tissuespecific regulation; however, some of these proteins have lost either their ability to bind m7G or eIF4G poising them as potential inhibitors or repressors of initiation (Joshi et al., 2005; Rhoads, 2009). eIF4E1 b and eIF4E1 c from Arabidopsis were found to bind eIF4G and to m7G-affinity resin and thus function biochemically in vitro as canonical cap-binding proteins (Patrick et al., 2014; Kropiwnicka et al., 2015). However, the double mutant eIF4E eIFiso4E is lethal suggesting that eIF4E1b and eIF4E1c are not able to replace eIF4E in vivo (Callot and Gallois, 2014; Patrick et al., 2014).

Several laboratories made the simultaneous discovery that mutations in the genes encoding eIFiso4E or eIF4E confer naturally occurring virus resistance and prevent viral replication (Jiang and Laliberte, 2011; Wang and Krishnaswamy, 2012). Plants and many of their RNA viruses have co-evolved and a significant portion of this evolution appears to center on the use of eIF4F and eIFiso4F subunits by viruses for replication. Interestingly, neither Arabidopsis eIF4E1b nor eIF4E1c are recognized as virus resistance genes in contrast to dozens of examples for eIF4E and eIFiso4E (Robaglia and Garanta, 2006; Charron et al., 2008; Moury et al., 2013). Likely, other plants have multiple eIF4E/eIFiso4E genes, some of which may have evolutionary advantages for specific functions during stress or development.

The viral 5′ linked protein (VPg) of potyviruses was found to interact directly with eIF4E or eIFiso4E, as well as other translation factors (eIF4G, eIFiso4G, PABP, eIF4A, eEF1A) (Jiang and Laliberte, 2011; Wang and Krishnaswamy, 2012). A number of mutations in subunits of cap-binding complexes interfere with virus reproduction, yet these mutations do not appear to compromise host protein synthesis. This suggests that it is not the protein synthesis activity per se that confers virus resistance, but some other aspect that has yet to be discovered. There is interest in using these genes to engineer better virus resistance for economically important crops (Wang and Krishnaswamy, 2012; Moury et al., 2013; Kim et al., 2014a) and it is likely that virus/host co-evolution has shaped the roles of these initiation factors in plants (Moury et al., 2013).

Positive strand plant viral RNAs recruit eIF4F and/or eIFiso4F using structural elements in the 3′ UTRs termed 3′ cap-independent translation enhancers (3′CITES) (reviewed in Simon and Miller, 2013). These varied structural RNA elements appear to function as “cap substitutes” through direct interaction with eIF4F or eIFiso4F (or both). Plant viral 3′CITES are unlike the internal ribosome entry site (IRES) elements associated with animal and insect viruses that use internal initiation as their hallmark and vary in their initiation factor requirement (Komar et al., 2012; Jackson, 2013). Plant viral 3′CITES typically make use of RNA-RNA interactions that base pair a portion of the 3′CITE with a 5′ UTR loop (“kissing loop”) in a manner reminiscent of the 5′ to 3′ interactions of the canonical initiation process involving the 5′ cap and 3′ poly(A) tail (Simon and Miller, 2013). Additionally, some plant viral RNA 3′ UTRs use molecular mimicry by folding into structures that resemble tRNAs recruiting ribosomes directly (Simon and Miller, 2013). There is much to be learned from these interesting structures and the co-evolution of viruses and eIF4F/eIFiso4E host proteins. Since viruses are adept at co-opting host systems and using them to their advantage, it is likely that at least some host mRNAs may have elements similar to a 3′CITE.

eIF4E-Binding Proteins: Are they actors on the plant stage?

A major form of regulation of mammalian translation is through 4E binding proteins (4EBPs) that are regulated via phosphorylation by mammalian TOR (mTOR) in the PI3K-Akt signaling pathway that responds to many types of stress and environmental cues (Carrera, 2004; Richter and Sonenberg, 2005; Hernández et al., 2010). Phosphorylated mammalian 4EBPs dissociate from eIF4E, allowing it to interact with eIF4G to form a functional complex, whereas unphosphorylated 4EBPs bind to eIF4E and sequester it from interaction with eIF4G, thereby limiting eIF4F/cap-dependent initiation (Carrera, 2004; Richter and Sonenberg, 2005). Plants have a functional TOR system that senses metabolic states (Ren et al., 2012; Robaglia et al., 2012; Xiong and Sheen, 2012; Caldana et al., 2013; Dobrenel et al., 2013; Xiong et al., 2013; Xiong and Sheen, 2013, 2014), but appear to lack 4EBPs that regulate eIF4F complex formation (Verma and Chatterjee, 2009). Given the sub/nanomolar binding of the plant eIF4F and eIFiso4F subunits to each other, it seems unlikely that these complexes will dissociate once formed (Mayberry et al., 2011). Plants have proteins with canonical eIF4E binding sites that have been shown to bind to eIF4E or eIFiso4E, such as lipoxygenase 2 and BTF3 (beta subunit of the nascent polypeptide-associated complex (Freire et al., 2000; Freire, 2005); however, the role(s) of these protein interactions with plant cap-binding proteins is still unclear.

Phosphorylation of eIF4G/iso4G and eIF4E/iso4E

Although there are reports of multiple isoelectric states of wheat eIF4F/iso4F subunits, the effect on activity and the kinases involved have not been identified (Gallie et al., 1997). Neither eIF4F nor eIFiso4F subunits were targets of CK2, unlike eIF4B (Dennis and Browning, 2009). Only eIF4G was found to be phosphorylated in the phosphoproteome of the light to dark transition (Boex-Fontvieille et al., 2013). Given the importance of phosphorylation of eIF4E, 4E-BP and eIF4G in mammalian systems, it remains to be discovered if plants have evolved a different system for regulation of these subunits through phosphorylation, redox-sensitive structure regulation or other means.

Poly(A) Binding Protein

Although not an “official” initiation factor, PABP binds to the 3′ poly(A) tail of the mRNA and interacts with eIF4G and eIF4B, suggesting that the mRNA may be circularized at least transiently during initiation (Park et al., 2011). In mammals, PABPs have extensive roles in the nucleus and cytoplasm in mRNA processing, translation and degradation, as well as a role in miRNA-mediated processes (reviewed in Goss and Kleiman, 2013). Higher eukaryotes have multiple genes for PABP. In the case of X. laevis, PABP gene products have been shown to function similarly in translation, but are distinctly required for development indicating there may be mRNAs whose processing, expression or degradation requires a specific PABP (Gorgoni et al., 2011).

Plants have an extensive family of genes encoding PABP with considerable protein sequence diversity. The eight PAB genes in A. thaliana fall into four phylogenetic sub-groups with varying tissue specific expression (Le and Gallie, 2000; Belostotsky, 2003). In general, Arabidopsis and other plant PABPs have four RRM domains that consist of two a-helices and four anti-parallel β-sheets. A separately folded C-terminal domain called PABC is composed of 4 to 5 a-helices and contains a PABC interaction motif (PAM2) for protein-protein interaction. The solution structure of wheat PABC has a similar fold to the mammalian PABC domain and also contains the PABC-Interacting Motif (PAM-2) protein interaction domain (Siddiqui et al., 2007). A. thaliana PABC/PAM2 was shown to have multiple binding partners, several of which interfere with in vitro translation or are implicated in RNA metabolism (Wang and Grumet, 2004; Bravo et al., 2005; Siddiqui et al., 2007). Some plant PABPs have been reported to have two instead of four RRMs, suggesting specifically evolved functions for these proteins (Belostotsky, 2003). It is also well established that there can be multiple PABPs bound to the poly (A) tail of the mRNA at any given time, thus leading to a diversity of possible PABP molecules on one transcript, each perhaps recruiting different binding partners via the PAM2 interface. Adding further complexity is post-translational modification by phosphorylation, which also affects PABP's interactions with binding partners (Le et al., 2000).

Extensive biochemical analysis of wheat PABP has shown that the presence of eIF4G or eIF4B enhances its RNA binding activity and in turn the presence of PABP increases the affinity of the eIF4F complex for the cap and stimulates the ATPase and RNA helicase activities of eIF4A, eIF4F/eIFiso4F and eIF4B (reviewed in Gallie, 2014; Le et al., 1997; Wei et al., 1998; Bi and Goss, 2000; Luo and Goss, 2001; Khan and Goss, 2005; Cheng and Gallie, 2010). It has been further shown that plant eIF4G has an additional PABP binding domain that binds eIF4B in a competitive and mutually exclusive manner (Cheng and Gallie, 2010; Cheng and Gallie, 2013). This second domain is absent in mammals and yeast PABP. PABP is also implicated in viral replication (Smith and Gray, 2010) and plant PABP was shown to interact with the reverse transcriptase of turnip mosaic virus (TuMV) (Dufresne et al., 2008) and with the 3′UTR of tobacco etch virus (TEV) to promote internal initiation (Khan et al., 2008; Khan et al., 2009; Yumak et al., 2010; Iwakawa et al., 2012).

There are still many questions about the role of PABP in initiation, its interactions with various initiation factors and other proteins, such as the PAM2-domain containing Early Responsive to Dehydration 15 (ERD15) family members (Aalto et al., 2012). PABP function likely extends beyond initiation. For example, an Arabidopsis pab2 pab8 loss-of-function mutant maintained translation of late-embryogenesis mRNAs in young seedlings, leading to the suggestion that PABP contributes to turnover of abundant seed transcripts during early seedling development (Tiruneh et al., 2013).

eIF1 Group

This group is involved in the stimulation and assembly of the 43S PIC and includes eIF1 (called SUI1 in yeast) and eIF1A (formerly known as eIF4C). Both of these small factors (∼12–17 kDa) are single polypeptides and conserved across all eukaryotes. eIF1 has structural similarity to the initiation factor (IF)3 C-terminal domain in prokaryotes and eIF1A is the functional equivalent to prokaryotic IF1 (Valasek, 2012).

eIF1 and eIF1A

eIF1 binds near the peptidyl (P)-site of the 40S subunit and precludes Met-tRNAi Met bound to eIF2·GTP (the ternary complex) from being fully engaged in the peptidyl (P)-site of the 43S PIC until the initiation codon is accurately identified (Nanda et al., 2013; Martin-Marcos et al., 2014). eIF1Ahas an interesting structure with a folded central region that binds in the acceptor (A)-site of the 40S subunit; however, its N- and C terminal tails are unstructured and extend into the P-site. Similar to eIF1, eIF1A participates in preventing full P-site engagement of the Met-tRNAi Met until the correct initiation codon is identified (Nanda et al., 2013).

Recombinant wheat eIF1 was shown to function in formation of a multifactor complex (MFC) in vitro similar to that found in yeast and mammals (Asano et al., 2000; Dennis et al., 2009; Hinnebusch and Lorsch, 2012; Sokabe et al., 2012; Hinnebusch, 2014). The MFC, consisting of eIF1, eIF2, eIF3 and eIF5, presumably helps to organize these factors prior to binding to the 43S PIC. It also appears to stabilize binding of the ternary complex to the 40S subunit. Plant eIF1 interacts directly with eIF5 and the N-terminal domain of eIF3c (Dennis et al., 2009). On the other hand, eIF1A binds to the 40S subunit independently of the MFC. eIF1A purified from wheat germ substitutes biochemically for rabbit reticulocyte eIF1A suggesting a highly conserved function (Timmer et al., 1993). Overexpression of eIF1 and eIF1A have been reported to improve salt tolerance in plants (Rausell et al., 2003; Latha et al., 2004; Diedhiou et al., 2008; Sun and Hong, 2013), suggesting a role in stress acclimation.

eIF5 Group

Two members (eIF5, eIF5B) of this group function in the selection of the start site and engagement of codon-anticodon base pairing, whereas the third (eIF5A), functions in elongation. All three group members, eIF5, eIF5A and eIF5B are found in plants and other eukaryotes, suggesting ancient origin and conserved functions. eIF5 has GTPase activating protein function. eIF5B resembles prokaryotic IF2, but does not bind Met-tRNAi Met and functions to promote binding of the 60S subunit (subunit joining) which in turn promotes GTP hydrolysis and release of eIF5B as the last step of the initiation process. eIF5A (nee eIF4D), although initially designated an initiation factor, is the “imposter” in the group and promotes the peptidyl transferase reactions of poly-prolyl residues during elongation (Gutierrez et al., 2013) Given the role for eIF5A in elongation, it has been proposed to rename this factor eEF5 (Dever et al., 2014) (See section on Elongation Factors and Table 2.

eIF5

This protein promotes hydrolysis of GTP bound to the ternary complex during start site recognition (Jennings and Pavitt, 2010; Aitken and Lorsch, 2012; Hinnebusch and Lorsch, 2012; Valasek, 2012; Nanda et al., 2013; Hinnebusch, 2014). eIF5 has two functional domains, N-terminal (NTD) and C-terminal (CTD) with a linker connection (Conte et al., 2006; Wei et al., 2006). An “arginine finger” (Arg-15) required for GTPase activity is positioned near the N-terminus in an unstructured region. This unstructured region is free to interact with the GTP-binding region of eIF2y to promote GTP hydrolysis. In addition, the NTD has structural similarity to eIF1, which may play a role in events during initiation codon selection (Nanda et al., 2013). The eIF5 CTD contains a HEAT domain that interacts with eIF1, the NTD of eIF3c, and N-terminal tail of eIF2β to stabilize the MFC mentioned earlier that is formed by these factors (Nanda et al., 2013). In addition, the CTD of yeast eIF5 interacts with an unstructured region of eIF4G that is proposed to promote binding of the mRNA to the 43S PIC and assist in scanning and subsequent release of eIF1 (Singh et al., 2012). Whether this occurs with mammalian or plant eIF4G is not known. eIF5 has been shown to be released from mammalian PIC with eIF2·GDP and appears to have a role as GDP dissociation inhibitor during recycling of eIF2·GDP by eIF2B (Jennings et al., 2013). eIF5 from plants has received little attention, except studies that show that the wheat factor functions in the formation of a MFC in a manner enhanced by phosphorylation of members of the MFC by CK2 (Dennis et al., 2009). One of the in vitro CK2 sites of eIF5 was confirmed in the light/dark phosphoproteome (Boex-Fontvieille et al., 2013).

eIF5B

As the structural homolog of eubacterial IF2, eIF5B carries out a similar function in eukaryotes (Allen and Frank, 2007). Upon recognition of the initiation codon, a series of events including the release of eIF1 from its position near the P-site and hydrolysis of the GTP bound to ternary complex, leads to conformation changes in eIF2 (Allen and Frank, 2007). Atthis point eIF5B·GTP binds to the complex via contacts with the C-terminal tail of eIF1A and may stabilize the binding of the Met-tRNAi Met in the P-site (Pisareva and Pisarev, 2014). The binding of eIF5B·GTP likely displaces many of the associated factors (eIF2, eIF3 and eIF5) to open a surface for 60S subunit attachment. Hydrolysis of eIF5B·GTP is promoted by the GTPase activating activity of the 60S subunit, triggering release of eIF5B·GDP and eIF1A as the newly formed 80S complex is established (Allen and Frank, 2007). Mutations in mammalian eIF5B show this factor may play multiple roles during initiation in vitro (Pisareva and Pisarev, 2014). Pea eIF5B has been biochemically characterized as a heat stable protein with potential properties of a chaperone and binds to GTP as expected (Rasheedi et al., 2010; Suragani et al., 2011).

eIF6 Group

Designated as an initiation factor and the sole performer of this group, eIF6 interacts with the 60S subunit and functions in the prevention of premature association of the 60S ribosomal subunit with the 43S PIC. It also has a role in the assembly of the 40S and 60S ribosomal subunits (Miluzio et al., 2009; Brina et al., 2011). eIF6 was first discovered in wheat germ as a ribosome disassociation factor that bound 60S ribosomes (Russell and Spremulli, 1978, 1979, 1980) and subsequently identified in yeast (Si et al., 1997) and mammals (Valenzuela et al., 1982; Raychaudhuri et al., 1984).

In sequenced plant genomes, eIF6 is typically encoded by multiple genes; in the case of Arabidopsis a single eIF6 gene (AteIF6A) is broadly expressed and a second displays more regional and regulated transcript accumulation (AteIF6B) (Guo et al., 2011a). The role of eIF6 in subunit joining involves its interaction with the conserved ribosome-associated protein receptor of activated C kinase 1 (RACK1) (see section below on RACK1).

Table 2.

Elongation and Termination Factors of Arabidopsis

t02_01.gif

eIF6 also functions in ribosome biogenesis and the transport of ribosomal subunits from the nucleolus to the cytoplasm in a process that requires phosphorylation of a CK1 site that is conserved in AteIF6A, but lost in AteIF6B mutants (Guo et al., 2011a).

The Ribosome: the Prima Donna

The peptidyl transferase reaction is catalyzed by the ribosome, a highly evolutionarily conserved macromolecular complex of two subunits that is comprised of RNA and proteins (Yusupova and Yusupov, 2014). Without exception, the role of the small subunit of the ribosome isto decode the mRNA whereas the large subunit catalyzes the peptidyl transferase reaction (peptide bond formation). Decoding involves the A-, P- and exit (E)-site positions transiently occupied by tRNAs as they bring amino acids to transfer to the growing polypeptide chain and exit empty to be recharged.

Subunit composition

Ribosomes, their subunits, and rRNAs are measured in Svedberg (S) units corresponding to their sedimentation coefficient measured by ultracentrifugation. When joined together, cytosolic ribosomes of higher eukaryotes (including plant 40S and 60S subunits) sediment at 80S. The 40S subunit is formed with 18S rRNA and small ribosomal proteins (RPSs) and the 60S by the 5S, 5.8S, and 25–28S rRNAs and large ribosomal proteins (RPLs). The subunits of lower eukaryotes have the same four rRNA molecules and are therefore slightly smaller. The ribosomes of bacteria, mitochondria and plastids are significantly smaller, typically consisting of a 30S small subunit with a 16S rRNA and a 60S large subunit with 23S and 5S rRNAs and no 5.8S rRNA. The rRNAs of eukaryotes possess several expanded segments and variable regions relative to their bacterial counterparts. It was postulated that these expansion regions are associated with the more complex control of translation. Accompanying the rRNA distinctions are eukaryote-specific RPs, all of which are encoded in higher plants (Barakat et al., 2001). The remaining RPs fall into two groups of either eubacterial (found across kingdoms) or archaea/eukaryote-specific origin (Armache et al., 2010b, a). Atotal of 54 RPs are recognized in eubacteria, 79 in yeast, and 79- 80 RPs in higher eukaryotes. With the exception of the RPs that form a flexible lateral stalk of the large subunit, all are present in a single copy per ribosome (Yusupova and Yusupov, 2014).

Ribosome architecture

High-resolution crystal structure analyses confirm pronounced conservation of the three-dimensional structure of ribosomes between eubacterial, archaebacterial and eukaryotic kingdoms (Klinge et al., 2012; Voigts-Hoffmann et al., 2012; Yusupova and Yusupov, 2014). The larger mass of eukaryotic ribosomes has presented a greater challenge for obtaining crystals with high-quality diffraction characteristics. Consequentially, insights into eukaryotespecific structural features of ribosomes have been gleaned from cryo-EM structural analyses, including models at 38 Å (Verschoor et al., 1996) and at <10 Å resolution for translating wheat, yeast, insect, and mammalian ribosomes (Armache et al., 2010b, a). These models provide a wealth of insight into the position and structure of rRNAs and RPs.

Eukaryotic-specific RPs are located at several key positions within animal, yeast and wheat ribosomes, including the sites associated with decoding and tRNA binding, and mRNA exit on the 40S subunit. RPs specific to both subunits interact with the eukaryote-specific factor eIF3. The cryo-EM studies of insect and mammalian ribosomes emphasize the presence of rRNA expansion regions on the outer periphery that dynamically form RP-rRNA and rRNA-rRNA interactions (Anger et al., 2013). The wheat ribosome is more like that of yeast with a less extensive outer rRNA-protein layer. Further studies of plant ribosome architecture are needed to better appreciate kingdom-specific features as well as structural variations that might be associated with specific RP isoforms.

Interest in plant ribosomes, as well as other organisms, centers around several questions: Do ribosomes play specific roles in global translational activity or the translation of individual mRNAs? Is there ribosome heterogeneity due to differences in protein isoform composition or modification and if so, what is itsfunction(s)? Are ribosome biogenesis and protein synthesis tightly regulated as a means of energy conservation and does management of these investments pace growth during the diurnal cycle or under abiotic environment? Is a threshold level of ribosomes necessary for cellular and organismal homeostasis?

Cytosolic ribosomal proteins

Eighty RP gene families of two to five paralogous members were identified in the Arabidopsis genome by comparison to the amino acid sequences of animal, yeast and Archaea RPs (Barakat et al., 2001) (see Table 3). The vast majority of RPs are basic in charge (pl > 8.0) and ≤ 45 kDa in mass. There are, however, a handful of conserved acidic RPs (pl < 5). Eukaryotes have two RP gene families that encode small acidic phosphoproteins that dimerize and bind the larger RPP0 to form a flexible lateral stalk structure on the large ribosomal subunit. Higher plants have a RPP1 and RPP2 family, as well as a third acidic RP called RPP3 (Szick et al., 1998; Chang et al., 2005). This stalk structure promotes eEF2 binding and GTP hydrolysis in yeast (Gonzalo and Reboud, 2003) and is important in the binding of ribosome inactivating proteins, such as the ricin toxin (Li et al., 2013c).

Several mass spectrophotometric studies have explored the proteome of Arabidopsis ribosomes. Ribosomes purified by differential centrifugation yielded 31–33 of the putative 40S RPs and 48 of the putative 60S RPs, respectively (Chang et al., 2005; Giavalisco et al., 2005; Carroll et al., 2008; Piques et al., 2009; Turkina et al., 2011; Carroll, 2013). An analysis performed on ribosomes captured by immunopurification, thereby limiting contamination by organellar ribosomes and other co-sedimenting complexes, confirmed products from 204 of the estimated 232 functional RP genes of A. thaliana based on two or more prototype peptides (Hummel et al., 2012). This corresponded to 64 of the 80 putative RP families and included RACK1. Of these, 74 Arabidopsis RPs were positioned in a high-resolution 80S ribosome structure map relative to the rRNA structure (Armache et al., 2010b).

Ribosome heterogeneity

The biogenesis of a ribosome requires coordinated synthesis of rRNAs and RPs. In Arabidopsis, the 18S, 5.8S and 25S rRNA are encoded by the 45S rDNA genic repeat that is tandemly duplicated over 500 times on the short arms of chromosome 2 and 4, whereas the pre-5S rRNA is encoded by repetitive pericentromeric regions on chromosomes 3, 4 and 5 (Layat et al., 2012). The 18S, 5.8S and 25S rRNA precursor of Arabidopsis is sometimes referred to as the 35S pre-rRNA. The transcription of the Arabidopsis 45S rDNA units by RNA polymerase I is regulated by direct binding of TOR to the promoter region located in the intergenic region (spacer) between the 25S and 18S genes (Ren et al., 2011). The subsequent pre-rRNA processing pathway is a complicated pathway involving cleavage and nucleotide modification events. Synthesis of 5S rRNA by RNA polymerase III is regulated by mTOR in animals (Kantidakis et al., 2010); however, the regulation of plant 5S rRNA synthesis is not well characterized.

Arabidopsis RP genes are significantly co-regulated at transcriptional and post-transcriptional levels during development, in response to various stimuli and in some translational apparatus mutants. The coordinate transcriptional and posttranscriptional regulation of many RP genes reflects the presence of common cis-regulatory elements in gene promoters and features of mRNA 5′UTRs (Kawaguchi et al., 2004; Branco-Price et al., 2005; McIntosh and Bonham-Smith, 2006; Nicolaï et al., 2006; Tiruneh et al., 2013; Wang et al., 2013). Close inspection of Arabidopsis RP transcript accumulation data indicate that there is more than one RP transcription network regulated in response to carbon and nitrogen availability, as well as other environmental inputs (Sormani et al., 2011a; Wang et al., 2013). RP gene co-regulation was also noted when monitoring polysome-associated transcript levels. A coordinate shift of Arabidopsis RP mRNAs out of polysome complexes was observed in response to a number of environmental stresses (Kawaguchi et al., 2004; Branco-Price et al., 2005; McIntosh and Bonham-Smith, 2006; Nicolaï et al., 2006; Branco-Price et al., 2008; Pyl et al., 2012; Tiruneh et al., 2013; Wang et al., 2013). Conversely, coordinated up-regulation of the translation of a large majority of Arabidopsis RP mRNAs was recorded in two mutants of the translational apparatus (eif3h and rpl24b) (Tiruneh et al., 2013). Co-regulation of RP gene transcript accumulation and translation has also been noted in Chlamydomonas (Schmollinger et al., 2014).

The stereotype of a ribosome is that all are the same, but there is some evidence of specialized differences in cytosolic ribosomes of Arabidopsis and other plants that may contribute to the regulation of translation (Horiguchi et al., 2012; Hummel et al., 2012). Ribosome heterogeneity is predicted to be the consequence of ancestral genome duplication and subsequent neofunctionalization of members of some RP gene families as well as regulated post-translational modification of some RPs. For example, transcripts of Arabidopsis RP paralogs are regulated by environmental inputs including carbon, phosphate and metals (Hummel et al., 2012; Wang et al., 2013). RP transcript levels are also differentially regulated between cell types (e.g., (Mustroph et al., 2009). Other sources of ribosome heterogeneity include N-terminal methionine removal, N-terminal acetylation, methylation of lysine and proline residues and phosphorylation of serine and threonine residues of RPs (Bailey-Serres and Freeling, 1990; Bailey-Serres et al., 1997; Szick-Miranda and Bailey-Serres, 2001; Williams et al., 2003; Chang et al., 2005; Carroll et al., 2008; Turkina et al., 2011; Hummel et al., 2012; Boex-Fontvieille et al., 2013; Carroll, 2013). The functional consequence of ribosome heterogeneity is largely unknown, but may provide for a complex regulatory network that impacts translation at the global or mRNA specific level.

Table 3.

Cytosolic Ribosomal Protein Genes of Arabidopsisa

t03a_01.gif

Continued.

t03b_01.gif

Continued.

t03c_01.gif

Ribosomal protein phosphorylation

The most well studied phosphorylated RP is the 40S subunit protein RPS6, which is modified at multiple serine residues at its C-terminus. This region of the protein extends into the mRNA exit channel of the ribosome (Anger et al., 2013). In mammals, RPS6 is phosphorylated by p70S6k, whose activity is mediated by the mTOR kinase which also phosphorylates other proteins that regulate translation (Zoncu et al., 2011). The direct impact of RPS6 phosphorylation on mammalian translation may be negligible, but provides an effective readout for p70S6k activity in actively dividing cells, which promotes efficient translation of mRNAs with a polypyrimidine track at their 5′ end (5′TOP). This feature is a characteristic of mRNAs encoding RPs and a number of core translation factors in mammals, but there is only limited evidence of functional 5′TOPs in plants (Jiménez-López et al., 2011). In Arabidopsis, RPS6 phosphorylation is promoted during the day (Turkina et al., 2011; Boex-Fontvieille et al., 2013) and in response to auxin and cytokinin (Turck et al., 2004), but is repressed by hypoxia (Chang et al., 2005). In monocots, RPS6 is phosphorylated in embryos during germination (Beltrán-Peña et al., 2002) and its phosphorylation rapidly declines following hypoxia, heat shock and singlet oxygen treatment (Williams et al., 2003; Khandal et al., 2009). The RPS6 kinase of Arabidopsis, AtS6K1, is important in regulating cell division and growth (Henriques et al., 2010; Shin et al., 2012). New data suggest a non-ribosomal function of RPS6 in epigenetic regulation of rDNA transcription in Arabidopsis (Kim et al., 2014c). Further clarification will require mutational analyses to determine if RPS6 phosphorylation is biologically significant or simply a hallmark of S6K activity in plants. Clearly there are many layers of S6K regulation yet to be explored and explained at the molecular level.

Most RPs assemble into pre-ribosomes in the nucleolus at a stoichiometry of one copy per ribosome. By contrast, the acidic proteins RPP1 and RPP2 complex in the cytoplasm with one another and then assemble onto the ribosome (Gonzalo and Reboud, 2003). The acidic proteins can be absent or present in multiple copies on the ribosome. Plant ribosomes possess a related third plant-specific protein called RPP3 (Szick et al., 1998). A source of heterogeneity of plant ribosomes is developmentally and environmentally regulated by modulation of RPP1, 2 and 3 levels and phosphorylation status (Bailey-Serres et al., 1997; Szick-Miranda and Bailey-Serres, 2001; Turkina et al., 2011; Boex-Fontvieille et al., 2013). The biological relevance of P-protein phosphorylation also deserves additional investigation.

Phosphoproteomic studies have also provided insight into the modulation of RP phosphorylation. In a non-targeted phosphoproteomics study, one or more isoforms of Arabidopsis RPs displayed distinct patterns of phosphorylation according to availability of CO2 and light (Boex-Fontvieille et al., 2013). This included significant quantitative differences in phosphorylation state of RPS6A, RPS6B, RPL13D and RPL14A. Clearly further work on the functional consequences of RP phosphorylation is needed to better understand the complex interplay of signaling with protein modification and translational control in plants.

RACK1, A Ribosome Interacting Player

RACK1 is an interesting protein that is soluble, plasma-membrane-associated or ribosome-bound via interactions with the 18S rRNA and several 40S RPs (Valasek, 2012). RACK1 is stably associated with the 40S ribosomal subunit of Arabidopsis (Chang et al., 2005; Giavalisco et al., 2005; Carroll et al., 2008; Piques et al., 2009; Turkina et al., 2011; Hummel et al., 2012; Carroll, 2013), as in other eukaryotes. This protein has a seven bladed β-propeller domain that allows it to act as a scaffold, in a manner homologous to the heterotrimeric G protein Gβ subunit. RACK1 is involved in diverse signaling events as well as in translation (Gandin et al., 2013a). Its roles in mammals and yeast include recruitment of the protein kinase C that phosphorylates eIF6 to promote its release from the 60S. This event must take place before the joining of the 40S and 60S subunits can occur at the end of the initiation phase. Interestingly, Arabidopsis eIF6A/B appear to have both lost this protein kinase C phosphorylation site and only eIF6A retains a CK1 phosphorylation site (Guo et al., 2011a). RACK1 may have additional functions associated with protein synthesis, including recruitment of eIF3, regulation of RP synthesis, and promotion of the turnover of improperly folded nascent proteins (Gandin et al., 2013b). These distinct roles may involve different kinases recruited to the RACK1 scaffold. RACK1 was connected to the activity of miRNA in humans, C. elegans and Arabidopsis (Speth et al., 2013).

There are three RACK1 paralogs in Arabidopsis. All three Arabidopsis RACK1s are detected in ribosomes (Chang et al., 2005; Giavalisco et al., 2005; Carroll et al., 2008; Piques et al., 2009; Turkina et al., 2011; Hummel et al., 2012; Carroll, 2013), functionally complement a CPC2/RACK mutant of yeast, and interact with eIF6 (Guo et al., 2011a). Interestingly, single and multiple RACK1 mutants cause a variety of developmental abnormalities and enhance responsiveness to abscisic acid (ABA) (Guo et al., 2009; Guo et al., 2011b). Double mutants of rack1a rack1b are hyper-sensitive to anisomycin, an inhibitor of peptide elongation and display slightly reduced levels of 80S ribosomes under normal growth conditions and following ABA treatment (Guo and Chen, 2008). The multiple locations and functions of RACK1 makes interpretation of the double mutant phenotypes difficult. For example, RACK1s participates in pre-miRNA processing via interaction with SERRATE, a partner of DICER-LIKE 1 and the nuclear-cap binding complex (CBP20/80) in Arabidopsis (Speth et al., 2013; Raczynska et al., 2014). This apparent nuclear role of RACK1 contrasts to its invovlement with miRNAs in C. elegans, which is at the level of recruitment of the Ago2-miRNA silencing complex to polysomes for translational inhibition (Jannot et al., 2011). An unresolved question is whether ribosome-associated RACK1 functions in ALTERED MERISTEM PROGRAM 1 (AMP1)/AGO1/ miRNA-mediated translation repression in Arabidopsis (Li et al., 2013b). In summary, plant RACK1 is ribosome-associated and functions in a conserved manner but also has extra-ribosomal functions that may be plant-specific.

Ribosomal protein mutants

Over 20 RP gene mutants of Arabidopsis have been characterized (reviewed by Byrne, 2009; Horiguchi et al., 2012; Roy and von Arnim, 2013). Often, single or multiple loss-of-function mutations for individual RPs result in embryo-lethality or pleiotropic developmental phenotypes affecting organ size or shape. These include asymmetric or pointed first leaves and reduced rosette size. In many cases RP mutants display phenotypes related to defects in auxin-mediated processes. At the mechanistic level, there are at least four possible causes of RP mutant phenotypes: (1) insufficient ribosomes affecting mRNAs equally or specifically (2) non-functional ribosomes, (3) a requirement for a distinct ribosome form for translation of specific mRNAs, or (4) an extra-ribosomal function of the protein (reviewed by Horiguchi et al., 2012).

Ribosome insufficiency, for example, could arise when reduced levels of a specific RP limits the biogenesis of a ribosomal subunit (Horiguchi et al., 2012). Phenotypes associated with RP mutants, such as smaller plant rosette size could be the consequence of reduced ribosome biogenesis. The synthesis of both subunits is tightly coordinated within the nucleolus, culminating in export of individual subunits to the cytoplasm. The co-expression of multiple RP gene paralogs in the same cell-type may limit ribosome insufficiency. However, reduction in a core ribosome component could limit overall ribosome numbers, rather than just the stoichiometry of an individual subunit. This could be important, since ribosome levels may be tightly regulated to meter the amount of energy consumed in translation at specific developmental states (i.e., rapidly dividing versus differentiated cells) or under non-favorable environmental conditions. Indeed, the defects in cellular expansion of Arabidopsis leaves, a prominent phenotype of RP and ribosome biogenesis mutants, might be attributed to global reduction of ribosomes (Roy and von Arnim, 2013).

In the second scenario, RP mutants may not disrupt ribosome biogenesis but the subunits or complexes that form might be defective in overall activity or a specific function. This could occur if individual RPs have a specific role in translation. For example, studies of RPL24 indicated its importance in translation of mRNAs with small uORFs. RPL24 was also shown to be important in the intricate regulation of initiation of translation on CaMV 35S mRNA (reviewed by Roy and von Arnim, 2013). Levels of RPL4 and RPL5 were recognized as critical for translation of uORF-containing mRNAs encoding proteins important for auxin responses (Rosado and Raikhel, 2010; Rosado et al., 2012).

The third possibility is that ribosome heterogeneity, due to the product of a specific RP gene paralog, is necessary for translation of a sub-set of transcripts. This last concept was detailed by Horiguchi et al. (2012), but definitive examples of RP gene paralogs of distinct function remain limited. A possible example is provided by the Arabidopsis RPL10 paralogs, which appear to have non-redundant functions in male gametophyte development (Falcone Ferreyra et al., 2010; Falcone Ferreyra et al., 2013). However, it is necessary to rule out the possibility that RPL10 may have an extra-ribosomal function, as shown for a number of RPs in diverse eukaryotes (Warner and McIntosh, 2009; Xue and Barna, 2012).

Extra-ribosomal function has been suggested for several Arabidopsis RPs as well as RACK1. An example of an extra-ribosomal function is the proposed role played by RPS6 in the regulation of transcription of rDNA and some RP gene transcripts in Arabidopsis (Kim et al., 2014c). This function involves direct interaction of non-phosphorylated RPS6 with Histone Deacetylase 2B (HD2B), which suppresses rDNA transcription. It was hypothesized that phosphorylation of free RPS6 could reduce HD2B inhibition, thereby promoting rDNA transcription or processing. If regulated by TOR as proposed, this could place ribosome biogenesis and translational regulation under unified control (Kim et al., 2014c).

To move forward in our understanding of plant ribosomes there needs to be further consideration of whether limitation, excess, or modification of individual RPs modulates ribosome biogenesis or impacts translation of specific mRNAs. The use of gene silencing constructs equipped with inducible promoters or targeted gene editing as well as examinations limited to specific cells may aid in this challenge. Significant advancements would be generated by further structural analyses of 80S ribosomes or subunit-initiation/ elongation factor complexes of plant ribosomes.

Ribosomes and energy for their synthesis

The biogenesis and activity of ribosomes requires a considerable investment in energy to power the synthesis of RPs and rRNAs. In rapidly dividing cells, the synthesis of rRNAs and RPs necessary for ribosome biogenesis may utilize more than half of all cellular energy, as each amino acid addition to a nascent peptide consumes at least four NTP molecules: (2 ATP for generating each amino-acyl tRNA and 2 GTP for each elongation event) (Figure 2). For ribosome biogenesis there is the additional energy outlay for rRNA synthesis. It therefore is not surprising that both ribosome biogenesis and global levels of translation are central to energy management (Piques et al., 2009; Pyl et al., 2012; Pal et al., 2013). Situations that limit ATP and GTP availability such as hypoxia, unanticipated darkness and extended nighttime limit RP mRNA translation in Arabidopsis (Branco-Price et al., 2008; Piques et al., 2009; Pal et al., 2013). In seedlings, cytosolic RP mRNAs account for ∼10% of total cellular mRNA (Branco-Price et al., 2008). These transcripts are stable but rapidly translationally repressed during hypoxia due to sequestration in aggregates of oligouridylate binding protein 1C (UBP1C) (Sorenson and Bailey-Serres, 2014). This sequestration is quickly reversed upon reoxygenation, facilitating energy management during stress events.

Figure 2.

Overview of the steps of plant cytoplasmic translation elongation and termination cycles.

The elongating ribosome binds the incoming eEF1A·GTP·aa-tRNA in the A-site. If there is a match between the codon and anticodon of the tRNA, GTP hydrolysis occurs and eEF1A·GDP exits. Peptide bond formation occurs at the peptidyl transferase site; this reaction is mediated by the ribosome. eEF2·GTP binds and hydrolysis of GTP promotes translocation of the mRNA by three nucleotides, moving the now empty tRNA into the E-site, the newly elongated peptide·tRNA into the P-site, generating an empty A-site ready to accept another eEF1A·GTP·aa-tRNA. eEF1A·GDP requires the action of eEF1 B to exchange GDP for GTP. eEF2 does not require a guanine exchange factor to acquire another GTP molecule. It is clear that each step of elongation is expensive in energy. Two GTP are required in the ribosome during elongation and each incoming eEF1A·GTP·aa-tRNA requires the functional equivalent of two ATP molecules to activate the amino acid and add it to the tRNA acceptor arm site. The AMP formed in this process requires two ATP to regenerate back to ATP; thus even though one ATP is consumed in the aminoacylation reaction, two ATP are ultimately consumed. The arrival of the termination codon in the A-site triggers the binding of the eRF1·eRF3·GTP complex into the A-site. Upon GTP hydrolysis, the eRF3·GDP is released. ABCE1 binds at the A-site to the remaining eRF1, promoting release of the polypeptide. Subsequent ATP hydrolysis by ABCE1 dissociates the ribosomal subunits, releasing ABCE1, eRF3, the deacetylated tRNA in the P-site and the mRNA. Note that the factors and ribosomal subunits are not to scale.

f02_01.tif

RP mRNA translation in animals is largely mediated by mTOR activity, the presence of a 5′TOP, and the RNA binding protein La-related protein 1 (Thoreen et al., 2012; Tcherkezian et al., 2014). A characteristic of many other mammalian mRNAs that require mTOR activity is extensive secondary structure within their 5′ leader sequences. In the case of higher plants, it is not clear yet if coordinate regulation of RP mRNA translation is TOR or 5′TOP regulated. Arabidopsis RP mRNAs typically have GC-rich untranslated leaders (Kawaguchi et al., 2004; Branco-Price et al., 2005) and some have termini reminiscent of 5′TOPs. Whether or not a specific mRNA sequence or feature (i.e. structure) is involved, the manipulation of TOR levels in Arabidopsis influences overall levels of polysomes (Deprost et al., 2007). RNA binding proteins may also be a factor, as translation of a large number of RP transcripts was enhanced at subfreezing temperatures (4°C) by the RNA chaperone Cold Shock Protein 1, which has double-stranded RNA helicase activity (Juntawong et al., 2013). In sum, ribosome biogenesis is highly regulated due to the energy investment in both the transcription of rRNA and translation of RP mRNAs. Further study is needed to clarify the connections of these processes to TOR and S6K regulated energy sensing.

THE DRAMA OF INITIATION

The actors introduced in the previous section, initiation factors eIF1, eIF1A, eIF2, eIF3, and eIF5, come together on the 40S subunit to form the 43S PIC. This complex interacts with the mRNA and its associated factors (eIF4s) to form a 48S complex that is competent to search in the 5′ to 3′ direction for the initiation codon using the ATP-dependent scanning model proposed by Kozak (Kozak, 1978, 1980). The selection of the initiation codon depends upon its nucleotide sequence context and possibly other features in the mRNA. Upon selection of the initiation codon, a series of molecular events occurs that transforms the open scanning form of the 48S scanning complex to the closed form that is ready to engage the 60S subunit (Asano, 2014). This completes the initiation phase with an elongation competent 80S ribosome at the start of the desired ORF.

Formation of the 43S Pre-Initiation Complex

The 40S subunit, ternary complex (eIF2·GTP·Met-tRNAiMet), eIF1, eIF1A and eIF3 interact to form the 43S PIC. The ternary complex, eIF1, eIF1A, eIF3 and eIF5 can also form the MFC prior to interaction with the small ribosomal subunit. MFC formation in yeast promotes assembly and stability of the 43S PIC (Hinnebusch et al., 2007). The MFC has been shown in vitro to form in yeast (Asano et al., 2000), mammals (Sokabe et al., 2012) and plants (Dennis et al., 2009), suggesting that these protein interactions are part of a conserved mechanism.

Models for mRNA Binding of the eIF4s

The canonical model begins with mRNA interacting with the cap-binding complex through the eIF4E subunit, which is complexed with eIF4G. eIF4G then serves as the scaffold for assembly of eIF4A, PABP and eIF4B. This mRNA-factor complex is thought to then unwind the mRNA in an ATP-dependent manner for interaction with the 43S PIC. Since eIF4A is not a processive helicase, it is not clear exactly how an unwound region is initiated and maintained to enable ribosome binding. A more recent model of initiation (Aitken and Lorsch, 2012), places the eIF4s directly on the 43S PIC. In this scenario, the mRNA is subsequently recruited and unwound on the 40S subunit directly channeling the transcript. eIF4F/eIF4A could be bound to the mRNA (via the 5′ cap or other RNA binding regions on eIF4G) as a “chaperone” which facilitates its interaction with 43S PIC associated factors such as eIF4B, eIF3 and/or eIF5. This model would explain a number of protein-protein interactions that are known to occur in yeast (e.g. eIF4G-eIF3, eIF4G-eIF5, eIF4B-40S subunit). However, some of these interactions have yet to be shown to occur in other eukaryotes (e.g. eIF4G-eIF5) and further biochemical analysis is needed to confirm the myriad of protein-protein interactions in the 43S PIC·mRNA/eIF4s complex and when/where they occur during the initiation process. Whichever model(s) proves to be true, the key aspect of the process is the relaxation of secondary structure in the 5′ region of the transcript to facilitate ribosome binding, scanning, and eventually initiation codon recognition.

Start Site Recognition

Once the 43S PIC associates at the 5′ end of the mRNA, scanning proceeds from 5′ to 3′ until a start codon is selected (Kozak, 1986; Asano, 2014). This is facilitated by binding of eIF1 to the “open” or scanning form of the 43S PIC that is stabilized by contacts with the N-terminal tail of eIF2ß (Nanda et al., 2013). The zinc-binding domain in the C-terminus of eIF5 lies in close proximity to eIF1 and displaces the zinc-binding domain of eIF2ß. This close proximity allows the N-terminal tail of eIF5 with its arginine finger required to interact with eIF2 and stimulate the GTPase activity of eIF2y. The N-terminal tail of eIF5 prevents Pi release from the eIF2 ternary complex from this “open” conformation during the scanning process. When the scanning complex encounters the initiation codon in the suitable context in the P-site of the 40S subunit, the formation of the codon/anticodon base pair promotes full engagement of the Met-tRNAiMet. This disrupts eIF1 interaction with N-terminal tail of eIF2ß and results in eIF1 release. The eIF2ß N-terminal tail then interacts with the C-terminal domain of eIF5. The N-terminal domain of eIF5 is then able to interact with the C-terminal tail of eIF1A, which promotes the release of Pi from the ternary complex resulting in scanning arrest at a suitable initiation codon and conversion to a “closed” PIC (Asano, 2014; Hinnebusch, 2014; Saini et al., 2014).

A suitable initiation codon context is an A residue and to a lesser extent a guanine (G) residue at position -3 and a G residue at position +4 relative to the A+1UG codon of the mRNA. It is thought that nucleotides surrounding the start codon help to engage the closed PIC conformation as the AUG codon is recognized (Hinnebusch and Lorsch, 2012; Asano, 2014; Hinnebusch, 2014). The A at position -3 corresponds to the first nucleotide of the E-site of the 40S subunit and is occupied by eIF2 as the codon-anticodon interaction is established in the P-site. In Arabidopsis plants exposed to dehydration stress, transcripts that were better associated with polysomes during the stress were enriched in A nucleotides just upstream of the start codon (Kawaguchi and Bailey-Serres, 2005). A recent study of Arabidopsis 5′UTRs further showed that the positions of A residues in the -1 to -5 region from the AUG were highly correlated with translational efficiency and uracil (U) residues in the same region were negatively correlated (Kim et al., 2014b). These results suggest that the region 5′ to the AUG in Arabidopsis strongly influences translational efficiency in plants (Kim et al., 2014b). mRNAs with a 5′UTR that was shorter than average (125 nt) and had low potential for secondary structure formation had higher levels of ribosome occupancy. Consistently, the G+C nucleotide content of the 5′UTR was inversely correlated with translational activity during a variety of environmental stresses including dehydration, hypoxia and darkness (Branco-Price et al., 2005; Kawaguchi and Bailey-Serres, 2005; Juntawong and Bailey-Serres, 2012).

Non-AUG codons

There are also rare examples of initiation at non-AUG codons on Arabidopsis mRNAs, including AGAMOUS, FCA and POLyG. The latter encodes a RNA polymerase targeted to the plastid or mitochondrion based on the AUG selected (Riechmann et al., 1999; Wamboldt et al., 2009; Simpson et al., 2010). Mutational studies that evaluated the ramifications of initiation codon context, secondary structure, 5′UTR length and presence of uORFs on the rate of initiation on the protein coding ORFs of plants have provided insight into use of an CUG triplet as a functional initiation codon for the FCA transcript (Simpson et al., 2010). Advances in nucleotide-level resolution of ribosome position (Liu et al., 2013; Juntawong et al., 2014) and in vivo secondary structure (Ding et al., 2014) are likely to yield additional examples of non-AUG initiation and information on the surrounding mRNA region that will provide new insight into flexibility in start site selection in plants.

Reinitiation involving uORFs

The presence of one or more short uORFs that precedes a mORF presents a special situation to the scanning ribosome. Based on the characterization of GCN4 mRNA translation in yeast, the length of the uORFs, the spacing between the uORFs and the mORF, and specific mRNA sequence features contribute to the subtle regulation of subsequent reinitiation events that determine amount of GCN4 synthesized (Valasek, 2012). In plants, the amino acid sequence of the uORF peptide can also contribute to the translational regulation (Rahmani et al., 2009; Jorgensen and Dorantes-Acosta, 2012; Roy and von Arnim, 2013; von Arnim et al., 2014). In the case of mRNAs with multiple ORFs (polycistronic), ribosomes will initiate in the normal manner at the first AUG in a suitable context and elongation will proceed. When the termination codon is encountered, the termination process that dissociates the ribosome subunits is likely to occur. If the uORF is short there may be lingering association of eIF3 with the 40S subunit and the reassembly of the MFCmay occur (Asano, 2014). In plants, this process is enhanced when the eIF3h subunit is present and phosphorylated by S6K in a TOR kinase-dependent manner (Schepetilnikov et al., 2013).

Assembly of the 80S ribosome, the final scene of initiation

Upon formation of the “closed” PIC, mammalian eIF5 is released in complex with eIF2·GDP. eIF5′s role at this point is as a GDP dissociation inhibitor for eIF2·GDP until eIF2B is able to stimulate the replacement of GDP with GTP. The function of mammalian eIF2B is crucial as it allows eIF2·GDP to exchange for GTP and acquire a new Met-tRNAiMet for participation in another round of initiation (Jennings and Pavitt, 2010; Jennings et al., 2013); however, as described above it is not clear what the role and importance of plant eIF2B are at this time. The release of eIF5/ eIF2·GDP opens the surface of the 40S for binding of the 60S subunit, whereas eIF5B·GTP facilitates the 60S ribosome joining through interactions with the C-terminal tail of eIF1A, and then eIF5B·GDP readily dissociates from the complex.

eIF1A plays a central role in the entire process of initiation. First, through its interactions with the eIF1 C-terminal tail to stabilize the “open” PIC by preventing Met-tRNAiMet to fully engage in the P-site. Second, upon arrival at the correct AUG, the C-terminal tail of eIF1A is displaced and interacts with eIF5 to promote the release of Pi generated by hydrolysis of eIF2·GTP by eIF5. Lastly, eIF1A facilitates the formation of the 80S ribosome and is the last initiation factor to exit after eIF5B·GTP. Thus, the 80S ribosome positioned at the correct initiation codon is now ready to move on to the next act, elongation.

ACT 2: ELONGATION

Translational elongation is an evolutionarily conserved progression of ribosome catalyzed polypeptide formation through mRNA decoding (see Figure 2 and Table 2). Once the subunit joining is complete with the Met-tRNAiMet in the P-site of the ribosome, the second codon in the A-site awaits interaction with the anticodon of an aminoacyl (aa)-tRNA coupled to eEF1A·GTP (Dever and Green, 2012). Appropriate codon-anticodon interactions at the A-site will stimulate the peptidyl transferase reaction that generates a peptide bond between the Met-RNAiMet and the aa-tRNA, leaving a deacylated tRNAiMet in the P-site. The subsequent translocation of the mRNA by one codon shifts the peptidyl-tRNA to the P-site and the deacylated tRNA to the E-site, freeing the A-site for the next appropriate aa-tRNA and continuation of the cycle (Dever and Green, 2012; Doerfel et al., 2013). Translocation is facilitated by eEF2·GTP binding and GTP hydrolysis.

The principal cast for this process includes the aa-tRNAs, eukaryotic elongation factor (eEF)1A (homolog of bacterial EF-Tu), eEF1B (homolog of bacterial EF-Ts), eEF2 (homolog of bacterial EF-G) and the ribosome. The role of eEF5 (nee eIF5A) in the elongation process is emerging, and like its prokaryotic homolog (EF-P) appears to involve elongation of amino acid sequences enriched in runs of proline and/or glycine (Doerfel et al., 2013; Gutierrez et al., 2013; Ude et al., 2013). Aminoacyl tRNA synthetases (aa-synthetases) participate backstage. These enzymes are encoded by a large family of nuclear genes in Arabidopsis that couple cognate tRNAs to their amino acids to form acetylated tRNA (aa-tRNA) in an ATP dependent reaction.

THE ACTORS IN ELONGATION

eEF1A

eEF1A is the ortholog of bacterial elongation factor-Tu (EF-Tu). This factor forms a ternary complex with GTP and an aa-tRNA, which it delivers to the peptidyl transferase center when the corresponding codon is present in the A-site. Initial loose binding is followed by a recognition event that involves the hydrolysis of GTP and structural rearrangements of the tRNA, eEF1A and the ribosome. eEF1A·GDP is then released for recycling by eEF1B, a complex with GEF activity that recovers eEF1A·GTP (described below).

eEF1A is a highly abundant protein that may constitute up to 1% of the total protein in a cell. The protein is encoded by four paralogs in Arabidopsis. Seed endosperm of the maize opaque 2 mutant has increased levels of eEF1A from multiple genes and is associated with improved lysine content (Lopez-Valenzuela et al., 2003; Lopez-Valenzuela et al., 2004). Interestingly, eEF1A has functions and interactions outside of its role in translation including association with cytoskeleton (which may reflect an association of the translation process with cytoskeleton anchors), nuclear export, proteolysis, apoptosis and viral propagation (Browning, 1996; Sasikumar et al., 2012). This factor is also known to participate in processes including export of tRNAs from the nucleus and the targeting of damaged and misfolded proteins to the proteasome (Sasikumar et al., 2012). EF1A is also reported to have interactions with the tombusvirus replication complex and the 3′ tRNA-like structure of turnip yellow mosaic virus (Matsuda et al., 2004; Li et al., 2009).

eEF1B

In prokaryotes, EF-Tu·GDP cannot recycle the GDP for GTP without assistance from EF-Ts. Similarly, eEF1A requires an exchange factor, eEF1B. In contrast to the single polypeptide EF-Ts, eEF1B is a complex of proteins that varies in complexity from eukaryote to eukaryote. eEF1B has three components in plants, eEF1Bα, eEF1Bß and eEF1By (Table 2), two in yeast and three in mammals (Sasikumar et al., 2012). In some organisms eEF1B also includes a valyl tRNA synthetase. Very little is known specifically about eEF1B from plants other than it has been purified from wheat germ (Lauer et al., 1984) and was shown to play a role in viral replication (Sasvari et al., 2011; Hwang et al., 2013), as have eEF1A (Matsuda et al., 2004; Li and Nagy, 2011) and cap-binding complex subunits (Wang and Krishnaswamy, 2012).

Both eEF1A and eEF1B are post-translationally modified by phosphorylation involving several kinases and by methylation, which may influence various activities such as interaction with actin (Lopez-Valenzuela et al., 2003). Presumably these modifications reflect highly complex mechanisms of regulation in eukaryotes (Le Sourd et al., 2006; Sasikumar et al., 2012). Phosphorylation of elongation factors under photosynthetic control was not reported for Arabidopsis (Boex-Fontvieille et al., 2013).

eEF2

eEF2 is the functional equivalent to EF-G of prokaryotes. Peptide bond formation occurs rapidly following acceptance of the aa-tRNA into the A-site of the peptidyl transferase center within the large ribosomal subunit. This region is largely comprised of rRNA and is highly conserved between prokaryotic and eukaryotic ribosomes, indicating that the process of peptide bond formation is quite ancient (Dever and Green, 2012). After the peptide bond is formed in the peptidyl transferase reaction catalyzed by the ribosome, it is necessary to move the now uncharged tRNA from the P-site into the E-site, freeing the A-site for the next incoming aa-tRNA·eEF1A·GTP. A GTP·eEF2 complex binds to the ribosome and its GTP hydrolysis promotes the movement of the mRNA·tRNA·tRNA hybrid forward by three nucleotides, coinciding with the movement of the P-site deacylated tRNA to the E-site and ejection of the deacylated-tRNA from the E-site.

eEF2 is post-translationally modified at a conserved histidine residue to dipthamide. This modification makes eEF2 the target for ADP-ribosylation by diphtheria-like toxins (Ortiz et al., 2006; Zhang et al., 2008a). The biological significance of this unusual modification is unknown despite its conservation across all eukaryotes and Archaea. Wheat eEF2 was shown to have this modification as evidenced by ADP-ribosylation by diphtheria toxin (Lauer et al., 1984). eEF2 is also a substrate for phosphorylation by the Ca2+/calmodulin-dependent eEF2 kinase (eEF2K), which reduces eEF2 association with the ribosome. The phosphorylation site in mammals is a conserved threonine residue (T56). The mammalian AMP kinase and mTOR-signaling pathways converge to inhibit Ca2+-dependent eEF2K activity, thereby limiting translational elongation under nutrient limiting conditions (Leprivier et al., 2013). Conversely, hypoxia in mammals promotes eEF2K phosphorylation and accumulation. Because eEF2 phosphorylation is Ca2+-regulated, it is thought to regionally fine-tune protein synthesis, such as in dendrites of activated neurons (Heise et al., 2014). When purified wheat germ eEF2 was phosphorylated with a mammalian Ca2+/calmodulin-dependent kinase, its activity in the in vitro translation system was reduced (Smailov et al., 1993). Although a plant eEF2 kinase has not been recognized, phosphoproteomic analyses focused on translation factors detected P-Ser558 of Arabidopsis eEF2 (Guillaume Tcherkez, personal communication). This site is conserved relative to Ser595 of mammals. Interestingly, phosphorylation of Ser595 by cyclin A in mammals promotes phosphorylation of Thr56 by eEF2K (Hizli et al., 2013). The finding that the AteEF2 (LOS1) is important for protein synthesis at low temperatures (Guo et al., 2002) hints that regulation of eEF2 activity is relevant to cold acclimation and likely other stress conditions.

eEF5 (nee eIF5A/eIF4D)

eEF5 was formerly known as eIF5A/eIF4D due to its initial report as a stimulator of Met-puromycin synthesis in vitro, a model assay for initiation. eEF5 was later recognized as a facilitator of elongation (Nanda et al., 2009) and confirmed as the functional and structural equivalent of elongation factor P (EF-P) of eubacteria. Both EF-P and eEF5 are involved in the efficient elongation of proteins with runs of proline or glycine residues (Doerfel et al., 2013; Gutierrez et al., 2013; Ude et al., 2013). Why certain combinations of amino acids pose difficulties during elongation is not fully understood, but at least for the ¡mino acid proline (lacking the hydrogen at the amino group) it may be due to structural constraints introduced in the peptide backbone by its presence.

eEF5 has features that distinguish it from EF-P and is truncated on its C-terminus relative to EF-P, which limits its contacts with the 60S subunit (Gutierrez et al., 2013). eEF5 is the only eukaryotic protein known to be post-translationally modified with hypusine, a modification derived from spermidine, which is required for its activity. Similarly, prokaryotic EF-P is modified by ß-lysylation, also a spermidine derivative (Allen and Frank, 2007; Bullwinkle et al., 2013). The hypusine/ß-lysine modification is postulated to help eEF5 to engage the ribosome and bring proline residues into closer proximity in the peptidyl transferase center for peptide bond formation (Gutierrez et al., 2013). Given this proposed function, it may be informative to evaluate the density of ribosomes in regions of mRNAs enriched in proline codons in genotypes that vary in eEF5 abundance and hypusination. eEF5 also appears to be modified by phosphorylation in the light/dark transition (Boex-Fontvieille et al., 2013).

A number of studies of plant eEF5 have indicated a role in stress responses (abiotic, pathogen, iron deficiency), growth and development (Wang et al., 2003; Chou et al., 2004; Hopkins et al., 2008; Ma et al., 2010; Lan and Schmidt, 2011; Wang et al., 2012). eEF5 was found to be associated with eEF2 in pumpkin phloem (Ma et al., 2010). In Arabidopsis, an eEF5 paralog (reported as eIF5A-2) is necessary for cytokinin-mediated promotion of protoxylem development in seedling roots through genetic interaction with Cytokinin Response 1 (CRE1), a histidine kinase that binds cytokinin and the phophotransferase AHP6, that negatively regulates signaling by cytokinin (Ren et al., 2013). Given that these processes appear unrelated to translation, eEF5 may have additional biological function(s) in plants; alternatively, these may represent downstream outcomes due to translation defects involving proteins with poly-prolyl or glycyl residues whose translation may depend upon this factor.

Compared to initiation in plant translation, there has been less work on the elongation process and its factors. Whether there will be aspects of elongation or its control that are specific to plants await further discovery.

ACT 3, THE FINALE: FACTORS AND EVENTS OF TERMINATION

Elongation ends when translocation places one of the three stop codons (UAA, UGA, or UAG) into the A-site of the ribosome. This initiates the termination phase, which ends with disengagement of the peptide from the ribosome (Dever and Green, 2012; Jackson et al., 2012). There are two eukaryotic release factors (eRF1 and eRF3, see Table 2 and Fig. 2) in plants, the same as in mammals. The fate of the translation complex upon termination is still lacking in molecular details. Termination is usually followed by ribosome release, but may be followed by reinitiation of translation after a short coding sequence (i.e., a uORF) (Roy and von Arnim, 2013). In the special case of premature termination at a nonsense codon (a termination codon 5′ of an EJC), degradation of the transcript occurs via the NMD pathway (see below).

Prior to the final “act”, a complex of release factors (RF) and GTP must form in the cytosol in preparation for interaction with the ribosome (see Table 2). eRF3·GTP binds to eRF1 which acts as a GTP dissociation inhibitor. When the elongating ribosome arrives at a stop codon on the mRNA, the eRF3·GTP·eRF1 complex is recruited to the A-site, preventing further entry of eEF1A·aa-tRNA complexes. Unlike prokaryotic termination factors that have specificity for one or more termination codons, the eukaryotic ternary complex of eRF3·GTP·eRF1 recognizes all three stop codons (UAA, UGA, UAG) by a little known mechanism (reviewed in Dever and Green, 2012; Jackson et al., 2012).

THE ACTORS IN TERMINATION

eRF1 and eRF3

eRF1 is evolutionarily related to bacterial RF1 and RF2, class 1 RFs. The structure of these proteins resembles a tRNA, allowing the N-terminal domain of the RF to dock in the A-site and directly interact with the stop codon (Dever and Green, 2012; Jackson et al., 2012). The high fidelity of this binding coupled with the GTPase activity of eRF3 promotes the peptidyl tRNA hydrolysis necessary to release the polypeptide from the P-site and from the ribosome (Dever and Green, 2012; Jackson et al., 2012). At the structural level, the N-terminal region of eRF1 binds the stop codon, the middle domain enters the peptidyl transferase center where it promotes the hydrolytic release of the polypeptide, whereas the C-terminal region interacts with eRF3. eRF3′s GTPase activity is necessary both to increase the rate of peptide hydrolysis by eRF1 and the efficiency of termination (Dever and Green, 2012; Jackson et al., 2012). The structure of the eRF3·GTP·eRF1 ternary complex on the ribosome was determined, revealing a number of features that suggest it has a very similar GTPase activation mechanism to the prokaryotic aa-tRNA·EF-Tu·GTP complex (des Georges et al., 2014). eRF1 is retained after termination and is important for recycling of the ribosome by recruiting the ABCE1/RIL1 protein (see below and Fig. 2) which functions with eIF6 in the dissociation of the ribosome into subunits for recycling (Pisarev et al., 2010). Yeast eRF1 has been shown to have additional functions that affect the cytoskeleton and cell cycle (Valouev et al., 2002) and appears to “moonlight” as observed for the eEFs (Le Sourd et al., 2006; Sasikumar et al., 2012)

Arabidopsis has three AteRF1 genes that encode functional RFs (Chapman and Brown, 2004). The overexpression of AteRF1-1 resulted in the silencing of AteRF1-1 and to some extent AteRF1-2 and AteRF1-3 causing a phenotype known as broomhead (altered spacing between inflorescence stems cause a broom-like appearance) and is associated with perturbations in cell division and cell elongation (Petsch et al., 2005). AteRF1-2 mRNA levels are induced by high glucose levels and AteRF1-2 overexpression lines display increased glucose-mediated repression of germination (Zhou et al., 2010b). These genotypes are also hypersensitive to paclobutrazol, an inhibitor of gibberellin biosynthesis, as well as abscisic acid. Consistently, T-DNA insertion mutants of AteRF1-2 showed resistance to gibberellin synthesis inhibitors during germination. It is not yet clear if the role AteRF1-2 plays in glucose sensing or phytohormone responses reflects its role in termination or some other cellular role. It is important to determine if the broomhead and other phenotypes associated with eRF1 mutants in Arabidopsis are related to translation or other processes. Interestingly, a mutant (Or) that produces an orange color in cauliflower heads (infloresence meristems) due to an increase in ß-carotene and encodes, a protein shown to interact with eRF1-2. The Or mutant displays altered petiole elongation and other developmental alterations suggesting a role for termination in developmental programs (Zhou et al., 2010c). Much more needs to be learned about plant termination and its actors.

NONSENSE MEDIATED mRNA DECAY: CURTAINS FOR SOME mRNAs

In special cases, termination can trigger mRNA decay (Belostotsky and Sieburth, 2009). This mechanism, termed nonsense mediated decay (NMD), provides quality control of mRNAs as they transit from the nucleus to active translation complexes. The process provides continuity between the nuclear process of intron splicing and cytoplasmic translation. A key feature in the process is the EJC, which is deposited just 5′ of exon-exon junctions following splicing, and serves as a talisman in the pioneering (first) round of translation of an mRNA. Following translational initiation, the elongating ribosome is thought to displace many of the RNA binding proteins bound to the mRNA as it translocates from codon to codon. If an EJC lies 3′ of a stop codon or the transcript has an unusually long 3′ UTR (>300 bp), then eRF3, responsible for termination and release of the nascent polypeptide, associates with UPF1 (helicase up-frameshift 1), a protein needed to initiate NMD. Two other proteins required for this process, UPF2 and UPF3, bind to the EJC after splicing. mRNAs with an EJC 3′ of the termination codon properly position UPF1-3 such that the destruction of the mRNA is triggered (Chang et al., 2007). NMD functions similarly in plants based on the presence of orthologs of NMD components and evidence of NMD coupled to the turnover of mRNAs with premature termination codons (Kerényi et al., 2008; Reddy et al., 2013). The targeting of alternatively spliced transcripts with premature termination codons for NMD provides an example of a mechanism coupled to translation that modulates mRNA abundance in response to environmental cues (Kalyna et al., 2012). Thus the half-life of an mRNA can be intimately entwined with its translation.

The many factors, complexes and processes involved in the temporal and spatial regulation of mRNA decay in plants have received limited attention until quite recently (Maldonado-Bonilla, 2014). It is important to understand the connection between translation and decay processes, including miRNA-mediated translational inhibition and mRNA turnover (Li et al., 2013b; Rogers and Chen, 2013).

RECYCLING: IS THERE AN ENCORE?

The emerging view is that termination is followed by “recycling”, efficient reuse of the ribosome. At this point in the translational process the 80S ribosome, mRNA and tRNA-polypeptide chain are still coupled. This requires that the two subunits of the ribosome dissociate and eRF1 as well as the deacylated tRNA be released. In prokaryotes ribosome recycling is promoted by EF-G and a dedicated ribosome recycling factor (RRF), present only in prokaryotes. Currently, it is thought that an essential protein, ATP-binding cassette E (ABCE1)/RNASE L INHIBITOR 1 (RLI1), conserved in eukaryotes and Archaea, promotes polypeptide release and ribosome recycling (Pisarev et al., 2010) in a process that requires ATP hydrolysis (Dever and Green, 2012; Jackson et al., 2012). Recent structural studies show that following eRF3·GDP release, ABCE1 binds to eRF1 and within the ribosome (Preis et al., 2014). This binding is associated with a dramatic conformational change in eRF3 that positions its central domain in the peptidyl transferase center, where it catalyzes the release of the polypeptide.

Other factors may be important in recycling of ribosomes on cytosolic mRNAs of eukaryotes. First, the proximity between the 3′ and 5′ ends of the message, fostered by the presumed interaction between PABP and eIF4s (Jackson et al., 2010; Valasek, 2012), may enable loosely associated 40S subunits to reform a PIC and recommence the initiation phase. There is, however, some debate about the importance of PABP/eIF4G interactions in the closed-loop mRNA model (Afonina et al., 2014). Studies with yeast and mammals (Dever and Green, 2012) point to a role of ABCE1/RLI1 in recruiting the MFC to the 40S subunit once the ribosome is dissociated. Interestingly, there is evidence from mammals that if eIF3, eIF1, eIF1A, and eIF2·tRNAiMet remain associated with the 40S subunit after termination then bidirectional scanning by the 40S or 80S complex occurs. Such a scenario would enable initiation at AUGs of downstream or upstream open reading frames (i.e., uORFs) that precede the ORF encoding the functional protein (Skabkin et al., 2013). The clever use of mimicry of tRNA shapes in some plant viral 3′ UTRs serves to recruit or recycle ribosomes, suggesting that recycling may be a common cellular event.

THE ACTORS IN RECYCLING

In addition to eRF1, the ABC-type ATPase ABCE1 is a key player in ribosome recycling. The Arabidopsis genome encodes two ABCE1 genes, which are characterized by an N-terminal Fe-S cluster and two nucleotide binding domains. A point mutation in a ABCE1/RLI1 ortholog in Cardamine hirsuta, a relative of Arabidopsis, converts the highly lobed leaf into a simple leaf and causes other downstream phenotypes (Kougioumoutzi et al., 2013). These findings suggest that ABCE1 plays an important role in numerous cellular developmental processes. Developmental dysfunctions including alterations in auxin homeostasis are quite frequent for mutants affecting ribosome biogenesis as described above. But caution is needed in interpreting these results, as it remains to be shown if ABCE1 has other roles or the efficiency of ribosome recycling is critical for development. Other proteins that act in the recycling of the translational apparatus in segue from termination to a new initiation event are unknown, with the exception of eIF6 which promotes subunit dissociation.

FUTURE PROSPECTS

The ease of isolation of mRNA and methods for global analyses of mRNA abundance has resulted in intense research on gene regulation in plants and other eukaryotes. Although, transcriptional regulation is frequently presumed to be the default mechanism that modulates steady-state transcript abundance, regulation that occurs at post-transcriptional levels including the processes that determine mRNA maturation, transport, stabilization, turnover and, in particular, translation have become increasingly apparent. In plants, these processes all contribute to dynamics in quantity, location and function of the gene product and are not readily discerned from steady-state transcript data. Technologies that enable the isolation of mRNAs associated with polysomes, such as translating ribosome affinity purification (TRAP) have helped to illuminate translational regulation of individual transcripts, particularly in Arabidopsis (Zanetti et al., 2005). Resolution of dynamics in mRNA translation will be enhanced by the ability to identify the position and frequency of ribosomes as they transit gene transcripts. This “ribosome profiling” strategy has been applied to examine changes in ribosome distribution along Arabidopsis mRNAs in seedlings upon illumination-triggering photomorphogenesis and during hypoxia (Liu et al., 2013; Juntawong et al., 2014). Translational dynamics occur in response to environmental stress, metabolites, and over the course of development (reviewed by Roy and von Arnim, 2013) and as a means for overall regulation of cellular energy over the diurnal cycle (Pal et al., 2013; Sulpice et al., 2014). Translational regulation may also be important in the tolerance of polyploidy in plants, as a comparison of total and polysomal mRNAs in the allopolyploid Glycine dolichocarpa indicated that selective translation contributes to dominance of expression of specific homoeologous genes as well as physically linked genes (Coate et al., 2014).

Further studies of the translational apparatus is needed, including the soluble factors, ribosomes and the cadre of RNA binding proteins that act as stagehands to fine-tune translational regulation. The use of genetic approaches to dissect the roles of the apparatus will most likely benefit from inducible constructs that reduce endogenous transcript levels or produce isoforms with specific features at controlled levels. In addition to a focus on endogenous mRNAs, the study of the performances of plant viruses in translation can be helpful. In the end, the data generated over the next decade will provide key insights, but is likely to also raise more enigmas. There are currently many questions about plant translation that are unanswered:

  • What is the role of eIF2 phosphorylation by GCN2 in regulating translation and are there other eIF2 kinases that might regulate global levels of translation?

  • Is there a plant version of eIF2B and what is its function?

  • What is the role of the plant-specific eIFiso4F and why did it evolve?

  • Are there other specific differences in plant initiation complexes compared to other eukaryotes?

  • What are the molecular interactions of the initiation factors with the ribosomes? Do they differ from other eukaryotes?

  • What factors besides eIF3h and the ribosome are important in uORF translation?

  • Is ribosome heterogeneity of biological significance?

  • Do specific ribosomal proteins regulate translation of individual gene transcripts or cohorts of mRNAs during development or in response to environmental cues?

  • What is the role of nutrient availability and TOR in ribosome biogenesis (including rRNA synthesis, RP mRNA transcription and translation), and other processes of translation?

  • What are the signals from chloroplast to nucleus that regulate coordinated synthesis of nuclear encoded photosynthetic proteins?

  • What RNA sequences or structures and RNA binding proteins contribute to differential translation, targeting, stability and trafficking of mRNAs?

  • What mechanisms sequester mRNAs into untranslatable pools, and how do they regain their ribosome loading?

  • What are the levels of interaction between chromatin, transcription, nuclear processing, translation, and mRNA turnover involving NMD, miRNA or general decay mechanisms?

As these questions are answered we will acquire a greater appreciation of the multi-dimensional and integrated performance within the cell nucleus and cytoplasm that culminate in the highly regulated “action drama” of protein synthesis in plants.

ACKNOWLEDGMENTS

We thank members of the Browning and Bailey-Serres laboratories who for more than twenty years have contributed to the advancement in understanding the importance of translational regulation and mechanisms of translation in plants. Particularly, we thank Albrecht von Arnim, Maureen Hummel and Angel Syrett for comments on this manuscript. We also thank Angel Syrett for the artwork. Our research related to translation is supported by the National Science Foundation (MCB1052530 and S-0000335) to K.S.B. and (IOS-1121626 and IOS-1238243) to J.B.-S.

REFERENCES

1.

M.K. Aalto , E. Helenius , T. Kariola , V. Pennanen , P. Heino , H. Hõrak , I. Puzõrjova , H. Kollist , and E.T. Palva ( 2012). ERD15--an attenuator of plant ABA responses and stomatal aperture. Plant Sci. 182, 19–28. Google Scholar

2.

R.D. Abramson , K.S. Browning , T.E. Dever , T.G. Lawson , R.E. Thach , J.M. Ravel , and W.C. Merrick ( 1988). Initiation factors that bind mRNA: a comparison of mammalian factors with wheat germ factors. J. Biol. Chem. 263, 5462–5467. Google Scholar

3.

Z.A. Afonina , A.G. Myasnikov , V.A. Shirokov , B.P. Klaholz , and A.S. Spirin ( 2014). Formation of circular polyribosomes on eukaryotic mRNA without cap-structure and poly(A)-tall: a cryo electron tomography study. Nuc. Acids Res. 42, 9461–9469. Google Scholar

4.

C.E. Aitken , and J.R. Lorsch ( 2012). A mechanistic overview of translation initiation in eukaryotes. Nat. Struct. Mol. Biol. 19, 568–576. Google Scholar

5.

G.S. Allen , and J. Frank ( 2007). Structural insights on the translation initiation complex: ghosts of a universal initiation complex. Mol. Microbiol. 63, 941–950. Google Scholar

6.

M.L. Allen , A.M. Metz , R.T. Timmer , R.E. Rhoads , and K.S. Browning ( 1992). Isolation and sequence of the cDNAs encoding the subunits of the isozyme form of wheat protein synthesis initiation factor 4F. J. Biol. Chem. 267, 23232–23236. Google Scholar

7.

M. Altmann , P.P. Müller , B. Wittmer , F. Ruchti , S. Lanker , and H. Trachsel ( 1993). A Saccharomyces cerevisiae homologue of mammalian translation initiation factor 4B contributes to RNA helicase activity. EMBO J. 12, 3997–4003. Google Scholar

8.

A.Z. Andreou , and D. Klostermeier ( 2013). The DEAD-box helicase eIF4A: paradigm or the odd one ou?t RNA Biol. 10, 19–32. Google Scholar

9.

A.Z. Andreou , and D. Klostermeier ( 2014). eIF4B and eIF4G jointly stimulate eIF4A ATPase and unwinding activities by modulation of the eIF4A conformational cycle. J Mol. Biol. 426, 51–61. Google Scholar

10.

A.M. Anger , J.P. Armache , O. Berninghausen , M. Habeck , M. Subklewe , D.N. Wilson , and R. Beckmann ( 2013). Structures of the human and Drosophila 80S ribosome. Nature 497, 80–85. Google Scholar

11.

J.P. Armache , A. Jarasch , A.M. Anger , E. Villa , T. Becker , S. Bhushan , F. Jossinet , M. Habeck , G. Dindar , S. Franckenberg , V. Marquez , T. Mielke , M. Thomm , O. Berninghausen , B. Beatrix , J. Söding , E. Westhof , D.N. Wilson , and R. Beckmann ( 2010a). Localization of eukaryote-specific ribosomal proteins in a 5.5-Å cryo-EM map of the 80S eukaryotic ribosome. Proc. Natl. Acad. Sci. U S A 107, 19754–19759. Google Scholar

12.

J.P. Armache , A. Jarasch , A.M. Anger , E. Villa , T. Becker , S. Bhushan , F. Jossinet , M. Habeck , G. Dindar , S. Franckenberg , V. Marquez , T. Mielke , M. Thomm , O. Berninghausen , B. Beatrix , J. Söding , E. Westhof , D.N. Wilson , and R. Beckmann ( 2010b). Cryo-EM structure and rRNA model of a translating eukaryotic 80S ribosome at 5.5-Å resolution. Proc. Natl. Acad. Sci. USA 107, 19748–19753. Google Scholar

13.

J.A. Arribere , and W.V. Gilbert ( 2013). Roles for transcript leaders in translation and mRNA decay revealed by transcript leader sequencing. Genome Res. 23, 977–987. Google Scholar

14.

K. Asano (2014). Why is start codon selection so precise in eukaryotes? Translation 2, e28387. Google Scholar

15.

K. Asano , J. Clayton , A. Shalev , and A.G. Hinnebusch ( 2000). A multifactor complex of eukaryotic initiation factors, eIF1, eIF2, eIF3, eIF5, and initiator tRNAMet is an important translation initiation intermediate in vivo. Genes & Dev. 14, 2534–2546. Google Scholar

16.

J. Bailey-Serres ( 1999). Selective translation of cytoplasmic mRNAs in plants. Trends Plant Sci. 4, 142–148. Google Scholar

17.

J. Bailey-Serres , and M. Freellng ( 1990). Hypoxic stress-induced changes in ribosomes of maize seedling roots. Plant Physiol. 94, 1237–1243. Google Scholar

18.

J. Bailey-Serres , R. Sorenson , and P. Juntawong ( 2009). Getting the message across: cytoplasmic ribonucleoprotein complexes. Trends Plant Sci. 14, 443–453. Google Scholar

19.

J. Bailey-Serres , S. Vangala , K. Szick , and C.H. Lee ( 1997). Acidic phosphoprotein complex of the 60S ribosomal subunit of maize seedling roots. Components and changes in response to flooding. Plant Physiol. 114, 1293–1305. Google Scholar

20.

M.L. Balasta , S.E. Carberry , D.E. Friedland , R.A. Perez , and D.J. Goss ( 1993). Characterization of the ATP-dependent binding of wheat germ protein synthesis initiation factors eIF-(iso)4F and eIF-4A to mRNA. J. Biol. Chem. 268, 18599–18603. Google Scholar

21.

A. Barakat , K. Szick-Miranda , I.F. Chang , R. Guyot , G. Blanc , R. Cooke , M. Delseny , and J. Bailey-Serres ( 2001). The organization of cytoplasmic ribosomal protein genes in the Arabidopsis genome. Plant Physiol. 127, 398–415. Google Scholar

22.

D.A. Belostotsky ( 2003). Unexpected complexity of poly(A)-binding protein gene families in flowering plants: Three conserved lineages that are at least 200 million years old and possible auto- and cross-regulation. Genetics 163, 311–319. Google Scholar

23.

D.A. Belostotsky , and L.E. Sieburth ( 2009). Kill the messenger: mRNA decay and plant development. Curr. Opin. Plant Biol. 12, 96–102. Google Scholar

24.

E. Beltrán-Peña , R. Aguilar , A. Ortíz-López , T.D. Dinkova , and E.S. De Jiménez ( 2002). Auxin stimulates S6 ribosomal protein phosphorylation in maize thereby affecting protein synthesis regulation. Physiol Plant 115, 291–297. Google Scholar

25.

L.A. Benkowski , J.M. Ravel , and K.S. Browning ( 1995a). mRNAbinding properties of wheat germ protein synthesis initiation factor 2. Biochem. Biophys. Res. Commun. 214, 1033–1039. Google Scholar

26.

L.A. Benkowski , J.M. Ravel , and K.S. Browning ( 1995b). Development of an in vitro translation system from wheat germ that is dependent upon the addition of eukaryotic initiation factor 2. Anal. Biochem. 232, 140–143. Google Scholar

27.

R. Benne , M. Kasperaitis , H.O. Voorma , E. Ceglarz , and A.B. Legocki ( 1980). Initiation factor eIF-2 from wheat germ: purification, functional comparison to eIF-2 from rabbit reticulocytes and phosphorylation of its subunits. Eur. J. Biochem. 104, 109–117. Google Scholar

28.

P. Beznosková , L. Cuchalová , S. Wagner , C.J. Shoemaker , S. Gunlšová , T. von der Haar , and L.S. Valášek ( 2013). Translation initiation factors eIF3 and HCR1 control translation termination and stop codon read-through in yeast cells. PLoS Genet. 9, e1003962. Google Scholar

29.

X.P. Bi , and D.J. Goss ( 2000). Wheat germ poly(A)-binding protein increases the ATPase and the RNA helicase activity of translation initiation factors eIF4A, eIF4B, and eIF-iso4F. J. Biol. Chem. 275, 17740–17746. Google Scholar

30.

X.P. Bi , J.H. Ren , and D.J. Goss ( 2000). Wheat germ translation initiation factor eIF4B affects eIF4A and eIFiso4F helicase activity by increasing the ATP binding affinity of eIF4A. Biochemistry 39, 5758–5765. Google Scholar

31.

E. Boex-Fontvieille , M. Daventure , M. Jossier , M. Zivy , M. Hodges , and G. Tcherkez ( 2013). Photosynthetic control of Arabidopsis leaf cytoplasmic translation initiation by protein phosphorylation. PLoS One 8, e70692. Google Scholar

32.

C. Branco-Price , R. Kawaguchi , R.B. Ferreira , and J. Bailey-Serres ( 2005). Genome-wide analysis of transcript abundance and translation in Arabidopsis seedlings subjected to oxygen deprivation. Ann. Bot. 96, 647–660. Google Scholar

33.

C. Branco-Price , K.A. Kaiser , C.J. Jang , C.K. Larive , and J. Bailey-Serres ( 2008). Selective mRNA translation coordinates energetic and metabolic adjustments to cellular oxygen deprivation and reoxygenation in Arabidopsis thaliana. Plant J. 56, 743–755. Google Scholar

34.

J. Bravo , L. Aguilar-Henonin , G. Olmedo , and P. Guzman ( 2005). Four distinct classes of proteins as interaction partners of the PABC domain of Arabidopsis thaliana poly(A)-binding proteins. Mol. Genet. Genomics 272, 651–665. Google Scholar

35.

D. Brina , S. Grosso , A. Miluzio , and S. Biffo ( 2011). Translational control by 80S formation and 60S availability: the central role of eIF6, a rate limiting factor in cell cycle progression and tumorigenesis. Cell Cycle 10, 3441–3446. Google Scholar

36.

K. Browning (2014). Cytoplasm: Translational apparatus. The Plant Sciences. Molecular Biology: Springer Reference 2014-02-13 03:17:23 UTC. Google Scholar

37.

K.S. Browning ( 1996). The plant translational apparatus. Plant Mol. Biol. 32, 107–144. Google Scholar

38.

K.S. Browning ( 2004). Plant translation initiation factors: it is not easy to be green. Biochem. Soc. Trans. 32, 589–591. Google Scholar

39.

K.S. Browning , D.R. Gallie , J.W. Hershey , A.G. Hinnebusch , U. Maitra , W.C. Merrick , and C. Norbury ( 2001). Unified nomenclature for the subunits of eukaryotic initiation factor 3. Trends Biochem. Sci. 26, 284. Google Scholar

40.

T.J. Bullwinkle , S.B. Zou , A. Rajkovic , S.J. Hersch , S. Elgamal , N. Robinson , D. Smil , Y. Bolshan , W.W. Navarre , and M. Ibba ( 2013). (R)-β-lysine-modified elongation factor P functions in translation elongation. J. Biol. Chem. 288, 4416–4423. Google Scholar

41.

E.A. Burks , P.P. Bezerra , H. Le , D.R. Gallie , and K.S. Browning ( 2001). Plant initiation factor 3 subunit composition resembles mammalian initiation factor 3 and has a novel subunit. J. Biol. Chem. 276, 2122–2131. Google Scholar

42.

M.S. Bush , A.P. Hutchins , A.M. Jones , M.J. Naldrett , A. Jarmolowski , C.W. Lloyd , and J.H. Doonan ( 2009). Selective recruitment of proteins to 5′ cap complexes during the growth cycle in Arabidopsis. Plant J. 59, 400–412. Google Scholar

43.

E.H. Byrne , I. Prosser , N. Muttucumaru , T.Y. Curtis , A. Wingler , S. Powers , and N.G. Halford ( 2012). Overexpression of GCN2-type protein kinase in wheat has profound effects on free amino acid concentration and gene expression. Plant Biotechnol. J. 10, 328–340. Google Scholar

44.

M.E. Byrne ( 2009). A role for the ribosome in development. Trends Plant Sci. 14, 512–519. Google Scholar

45.

C. Caldana , Y. Li , A. Leisse , Y. Zhang , L. Bartholomaeus , A.R. Fernie , L. Willmitzer , and P. Giavalisco ( 2013). Systemic analysis of inducible target of rapamycin mutants reveal a general metabolic switch controlling growth in Arabidopsis thaliana. Plant J. 73, 897–909. Google Scholar

46.

J. Callis ( 2014). The ubiquitination machinery of the ubiquitin system. The Arabidopsis Book 12, e0174. Google Scholar

47.

C. Callot , and J.L. Gallois ( 2014). Pyramiding resistances based on translation initiation factors in Arabidopsis is impaired by male gametophyte lethality. Plant Signal Behav 9, e27940. Google Scholar

48.

A.C. Carrera ( 2004). TOR signaling in mammals. J. Cell Sci. 117, 4615–4616. Google Scholar

49.

A.J. Carroll ( 2013). The Arabidopsis cytosolic ribosomal proteome: From form to function. Front. Plant Sci. 4, 32. Google Scholar

50.

A.J. Carroll , J.L. Heazlewood , J. Ito , and A.H. Millar ( 2008). Analysis of the Arabidopsis cytosolic ribosome proteome provides detailed insights into its components and their post-translational modification. Mol. Cell Proteomics 7, 347–369. Google Scholar

51.

I.F. Chang , K. Szick-Miranda , S. Pan , and J. Bailey-Serres ( 2005). Proteomic characterization of evolutionary conserved and variable proteins of Arabidopsis cytosolic ribosomes. Plant Physiol. 137, 848–862. Google Scholar

52.

L.Y. Chang , W.Y. Yang , K. Browning , and D. Roth ( 1999). Specific in vitro phosphorylation of plant eIF2α by eukaryotic eIF2α kinases. Plant Mol. Biol. 41, 363–370. Google Scholar

53.

Y.F. Chang , J.S. Imam , and M.F. Wilkinson ( 2007). The nonsensemediated decay RNA surveillance pathway. Annu. Rev. Biochem. 76, 51–74. Google Scholar

54.

B. Chapman , and C. Brown ( 2004). Translation termination in Arabidopsis thaliana: characterisation of three versions of release factor 1. Gene 341, 219–225. Google Scholar

55.

C. Charron , M. Nicolaï , J.L. Gallois , C. Robaglia , B. Moury , A. Palloix , and C. Garanta ( 2008). Natural variation and functional analyses provide evidence for co-evolution between plant eIF4E and potyviral VPg. Plant J. 54, 56–68. Google Scholar

56.

J.W. Checkley , L.L. Cooley , and J.M. Ravel ( 1981). Characterization of initiation factor eIF-3 from wheat germ. J. Biol. Chem. 256, 1582–1586. Google Scholar

57.

X. Chen ( 2010). Small RNAs - secrets and surprises of the genome. Plant J. 61, 941–958. Google Scholar

58.

Z. Chen , B. Jolley , C. Caldwell , and D.R. Gallie ( 2014). Eukaryotic translation initiation factor eIFiso4G is required to regulate violaxanthin de-epoxidase expression in Arabidopsis. J. Biol. Chem. 289, 13926–13936. Google Scholar

59.

S. Cheng , and D.R. Gallie ( 2006). Wheat eukaryotic initiation factor 4B organizes assembly of RNA and eIFiso4G, eIF4A, and PABP. J. Biol. Chem. 281, 24351–24364. Google Scholar

60.

S. Cheng , and D.R. Gallie ( 2007). eIF4G, eIFiso4G, and eIF4B bind the poly(A)-binding protein through overlapping sites within the RNA recognition motif domains. J. Biol. Chem. 282, 25247–25258. Google Scholar

61.

S. Cheng , and D.R. Gallie ( 2010). Competitive and noncompetitive binding of eIF4B, eIF4A, and the poly (A) binding protein to wheat translation initiation factor eIFiso4G. Biochemistry 49, 8251–8265. Google Scholar

62.

S. Cheng , and D.R. Gallie ( 2013). Eukaryotic initiation factor 4B and the poly(A)-binding protein bind eIF4G competitively. Translation 1, e24038. Google Scholar

63.

S. Cheng , S. Sultana , D.J. Goss , and D.R. Gallie ( 2008). Translation initiation factor 4B homodimerization, RNA binding, and interaction with poly(A)-binding protein are enhanced by zinc. J. Biol. Chem. 283, 36140–36153. Google Scholar

64.

C.M. Choi , W.M. Gray , S. Mooney , and H. Hellmann ( 2014). Composition, Roles, and Regulation of Cullin-Based Ubiquitin E3 Ligases. The Arabidopsis Book 12, e0175. Google Scholar

65.

W.C. Chou , Y.W. Huang , W.S. Tsay , T.Y. Chiang , D.D. Huang , and H.J. Huang ( 2004). Expression of genes encoding the rice translation initiation factor, eIF5A, is involved in developmental and environmental responses. Physiol. Plant 121, 50–57. Google Scholar

66.

J.E. Coate , H. Bar , and J.J. Doyle ( 2014). Extensive translational regulation of gene expression in an allopolyploid (Glycine dolichocarpa). Plant Cell 26, 136–150. Google Scholar

67.

M.R. Conte , G. Kelly , J. Babon , D. Sanfelice , J. Youell , S.J. Smerdon , and C.G. Proud ( 2006). Structure of the eukaryotic initiation factor (eIF) 5 reveals a role common to several translation factors. Biochemistry 45, 4550–4558. Google Scholar

68.

C. Cooke , and J.C. Alwine ( 1996). The cap and the 3– splice site similarly affect polyadenylation efficiency. Mol. Cell Biol. 16, 2579–2584. Google Scholar

69.

L. Cuchalova , T. Kouba , A. Herrmannova , I. Danyi , W.L. Chiu , and L. Valasek ( 2010). The RNA recognition motif of eukaryotic translation initiation factor 3g (eIF3g) is required for resumption of scanning of posttermination ribosomes for reinitiation on GCN4 and together with eIF3i stimulates linear scanning. Mol. Cell Biol. 30, 4671–4686. Google Scholar

70.

M.D. Dennis , and K.S. Browning ( 2009). Differential phosphorylation of plant translation initiation factors by Arabidopsis thaliana CK2 holoenzymes. J. Biol. Chem. 284, 20602–20614. Google Scholar

71.

M.D. Dennis , M.D. Person , and K.S. Browning ( 2009). Phosphorylation of plant translation initiation factors by CK2 enhances the in vitro interaction of multifactor complex components. J. Biol. Chem. 284, 20615–20628. Google Scholar

72.

D. Deprost , L. Yao , R. Sormani , M. Moreau , G. Leterreux , M. Nicolaï , M. Bedu , C. Robaglia , and C. Meyer ( 2007). The Arabidopsis TOR kinase links plant growth, yield, stress resistance and mRNA translation. EMBO Rep. 8, 864–870. Google Scholar

73.

A. des Georges , Y. Hashem , A. Unbehaun , R.A. Grassucci , D. Taylor , C.U. Hellen , T.V. Pestova , and J. Frank ( 2014). Structure of the mammalian ribosomal pre-termination complex associated with eRF1·eRF3·GDPNP. Nucl. Acids Res. 42, 3409–3418. Google Scholar

74.

T.E. Dever , and R. Green ( 2012). The elongation, termination, and recycling phases of translation in eukaryotes. Cold Spring Harb. Perspect. Biol. 4, 55–70. Google Scholar

75.

T.E. Dever , E. Gutierrez , and B.S. Shin ( 2014). The hypusine-containing translation factor eIF5A. Crit. Rev. Biochem. Mo.l Biol. 49, 413–425. Google Scholar

76.

C.J. Diedhiou , O.V. Popova , K.J. Dietz , and D. Golldack ( 2008). The SUI-homologous translation initiation factor eIF-1 is involved in regulation of ion homeostasis in rice. Plant Biol. (Stuttg) 10, 298–309. Google Scholar

77.

Y. Ding , Y. Tang , C.K. Kwok , Y. Zhang , P.C. Bevilacqua , and S.M. Assmann ( 2014). In vivo genome-wide profiling of RNA secondary structure reveals novel regulatory features. Nature 505, 696–700. Google Scholar

78.

T. Dobrenel , C. Marchive , M. Azzopardi , G. Clément , M. Moreau , R. Sormani , C. Robaglia , and C. Meyer ( 2013). Sugar metabolism and the plant target of rapamycin kinase: a sweet opera TOR? Front. Plant Sci. 4, 93. Google Scholar

79.

M.I. Dobrikov , E.Y. Dobrikova , and M. Gromeier ( 2012). Dynamic regulation of the translation initiation helicase complex by mitogenic signal transduction to eIF4G. Mol. Cell Biol. 33, 937–946. Google Scholar

80.

L.K. Doerfel , I. Wohlgemuth , C. Kothe , F. Peske , H. Urlaub , and M.V. Rodnina ( 2013). EF-P Is essential for rapid synthesis of proteins containing consecutive proline residues. Science 339, 85–88. Google Scholar

81.

N. Donnelly , A.M. Gorman , S. Gupta , and A. Samali ( 2013). The eIF2α kinases: their structures and functions. Cell Mol. Life Sc.i 70, 3493–3511. Google Scholar

82.

P.J. Dufresne , E. Ubalijoro , M.G. Fortin , and J.F. Laliberte ( 2008). Arabidopsis thaliana class II poly(A)-binding proteins are required for efficient multiplication of turnip mosaic virus. J. Gen. Virol. 89, 2339–2348. Google Scholar

83.

S. Echevarría-Zomeño , E. Yángüez , N. Fernández-Bautista , A.B. CastroSanz , A. Ferrando , and M.M. Castellano ( 2013). Regulation of translation initiation under biotic and abiotic stresses. Int. J. Mol. Sci. 14, 4670–4683. Google Scholar

84.

H. Ehsan , W.K. Ray , B. Phinney , X. Wang , S.C. Huber , and S.D. Clouse ( 2005). Interaction of Arabidopsis BRASSINOSTEROID-INSENSITIVE 1 receptor kinase with a homolog of mammalian TGF-β receptor interacting protein. Plant J. 43, 251–261. Google Scholar

85.

M.L. Falcone Ferreyra , A. Pezza , J. Biarc , A.L. Burlingame , and P. Casati ( 2010). Plant L10 ribosomal proteins have different roles during development and translation under ultraviolet-B stress. Plant Physiol. 153, 1878–1894. Google Scholar

86.

M.L. Falcone Ferreyra , R. Casadevall , M.D. Luciani , A. Pezza , and P. Casati ( 2013). New evidence for differential roles of L10 ribosomal proteins from Arabidopsis. Plant Physiol. 163, 378–391. Google Scholar

87.

S.A. Filichkin , and T.C. Mockler ( 2012). Unproductive alternative splicing and nonsense mRNAs: a widespread phenomenon among plant circadian clock genes. Biol. Direct 7, 20. Google Scholar

88.

S.A. Filichkin , H.D. Priest , S.A. Givan , R. Shen , D.W. Bryant , S.E. Fox , W.K. Wong , and T.C. Mockler ( 2010). Genome-wide mapping of alternative splicing in Arabidopsis thaliana. Genome Res. 20, 45–58. Google Scholar

89.

M.A. Freire ( 2005). Translation initiation factor (iso) 4E interacts with BTF3, the β-subunit of the nascent polypeptide-associated complex. Gene 345, 271–277. Google Scholar

90.

M.A. Freire , C. Tourneur , F. Granier , J. Camonis , A. El Amrani , K.S. Browning , and C. Robaglia ( 2000). Plant lipoxygenase 2 is a translation initiation factor-4E-binding protein. Plant Mol. Biol. 44, 129–140. Google Scholar

91.

D.R. Gallie (2007). Translational control in plants and chloroplasts. In Translational Control in Biology and Medicine, M.B. Mathews , N. Sonenberg , and J.W.B. Hershey , eds (Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press), pp. 747–774. Google Scholar

92.

D.R. Gallie ( 2014). The role of the poly(A) binding protein in the assembly of the cap-binding complex during translation initiation in plants. Translation 2, e959378. Google Scholar

93.

D.R. Gallie , and K.S. Browning ( 2001). eIF4G functionally differs from eIFiso4G in promoting internal initiation, cap-independent translation, and translation of structured mRNAs. J. Biol. Chem. 276, 36951–36960. Google Scholar

94.

D.R. Gallie , H. Le , C. Caldwell , R.L. Tanguay , N.X. Hoang , and K.S. Browning ( 1997). The phosphorylation state of translation initiation factors is regulated developmentally and following heat shock in wheat. J. Biol. Chem. 272, 1046–1053. Google Scholar

95.

V. Gandin , D. Senft , I. Topisirovic , and Z.A. Ronai ( 2013a). RACK1 function in cell motility and protein synthesis. Genes Cancer 4, 369–377. Google Scholar

96.

V. Gandin , G.J. Gutierrez , L.M. Brill , T. Varsano , Y. Feng , P. AzaBlanc , Q. Au , S. McLaughlan , T.A. Ferreira , T. Alain , N. Sonenberg , I. Topisirovic , and Z.A. Ronai ( 2013b). Degradation of newly synthesized polypeptides by ribosome-associated RACK1/c-Jun N-terminal kinase/eukaryotic elongation factor 1A2 complex. Mol. Cell Biol. 33, 2510–2526. Google Scholar

97.

G.M.D.J. Gaussand , Q. Jia , E. Van der Graaff , G.E. Lamers , P.F. Fransz , P.J.J. Hooykaas , and S. De Pater ( 2011). Programmed cell death in the leaves of the Arabidopsis spontaneous necrotic spots (sns-D) mutant correlates with increased expression of the eukaryotic translation initiation factor eIF4B2. Front. Plant Sci. 2, 9. Google Scholar

98.

P. Giavalisco , D. Wilson , T. Kreitler , H. Lehrach , J. Klose , J. Gobom , and P. Fucini ( 2005). High heterogeneity within the ribosomal proteins of the Arabidopsis thaliana 80S ribosome. Plant Mol. Biol. 57, 577–591. Google Scholar

99.

T. Gonatopoulos-Pournatzis , and V.H. Cowling ( 2014). Cap-binding complex (CBC). Bio chem. J. 457, 231–242. Google Scholar

100.

D.H. Gonzalez , and P. Giegé ( 2014). Biogenesis of the oxidative phosphorylation machinery in plants. From gene expression to complex assembly. Front. Plant Sci. 5, 225. Google Scholar

101.

P. Gonzalo , and J.P. Reboud ( 2003). The puzzling lateral flexible stalk of the ribosome. Biol. Cell 95, 179–193. Google Scholar

102.

B. Gorgoni , W.A. Richardson , H.M. Burgess , R.C. Anderson , G.S. Wilkie , P. Gautier , J.P. Martins , M. Brook , M.D. Sheets , and N.K. Gray ( 2011). Poly(A)-binding proteins are functionally distinct and have essential roles during vertebrate development. Proc. Natl. Acad. Sci. USA 108, 7844–7849. Google Scholar

103.

D.J. Goss , and F.E. Kleiman ( 2013). Poly (A) binding proteins: are they all created equal? Wiley Interdiscip. Rev. RNA. 4, 167–179. Google Scholar

104.

J. Guo , and J.G. Chen ( 2008). RACK1 genes regulate plant development with unequal genetic redundancy in Arabidopsis. BMC Plant Biol. 8, 108. Google Scholar

105.

J. Guo , Z. Jin , X. Yang , J.F. Li , and J.G. Chen ( 2011a). Eukaryotic initiation factor 6, an evolutionary conserved regulator of ribosome biogenesis and protein translation. Plant Signal. Behav. 6, 766–771. Google Scholar

106.

J. Guo , J. Wang , L. Xi , W.D. Huang , J. Liang , and J.G. Chen ( 2009). RACK1 is a negative regulator of ABA responses in Arabidopsis. J. Exp. Bot. 60, 3819–3833. Google Scholar

107.

J. Guo , S. Wang , O. Valerius , H. Hall , Q. Zeng , J.F. Li , D.J. Weston , B.E. Ellis , and J.G. Chen ( 2011b). Involvement of Arabidopsis RACK1 in protein translation and its regulation by abscisic acid. Plant Physiol. 155, 370–383. Google Scholar

108.

Y. Guo , L. Xiong , M. Ishitani , and J.K. Zhu ( 2002). An Arabidopsis mutation in translation elongation factor 2 causes superinduction of CBF/DREB1 transcription factor genes but blocks the induction of their downstream targets under low temperatures. Proc. Natl. Acad. Sci. USA 99, 7786–7791. Google Scholar

109.

E. Gutierrez , B.S. Shin , C.J. Woolstenhulme , J.R. Kim , P. Saini , A.R. Buskirk , and T.E. Dever ( 2013). eIF5A promotes translation of polyproline motifs. Mol. Cell 51, 35–45. Google Scholar

110.

N.G. Halford , S. Hey , D. Jhurreea , S. Laurie , R.S. McKibbon , Y. Zhang , and M.J. Paul ( 2004). Highly conserved protein kinases involved in the regulation of carbon and amino acid metabolism. J. Exp. Bot. 55, 35–42. Google Scholar

111.

Y. Hashem , G.A. des , V. Dhote , R. Langlois , H.Y. Liao , R.A. Grassucci , C.U. Hellen , T.V. Pestova , and J. Frank ( 2013). Structure of the mammalian ribosomal 43S preinitiation complex bound to the scanning factor DHX29. Cell 153, 1108–1119. Google Scholar

112.

C. Heise , F. Gardoni , L. Culotta , M. di Luca , C. Verpelli , and C. Sala ( 2014). Elongation factor-2 phosphorylation in dendrites and the regulation of dendritic mRNA translation in neurons. Front. Cell Neurosci. 8, 35. Google Scholar

113.

R. Henriques , Z. Magyar , A. Monardes , S. Khan , C. Zalejski , J. Orellana , L. Szabados , C. de la Torre , C. Koncz , and L. Bögre ( 2010). Arabidopsis S6 kinase mutants display chromosome instability and altered RBR1-E2F pathway activity. EMBO J. 29, 2979–2993. Google Scholar

114.

G. Hernández , and P. Vazquez-Pianzola ( 2005). Functional diversity of the eukaryotic translation initiation factors belonging to eIF4 families. Mech. Dev. 122, 865–876. Google Scholar

115.

G. Hernández , M. Altmann , and P. Lasko ( 2010). Origins and evolution of the mechanisms regulating translation initiation in eukaryotes. Trends Biochem. Sci. 35, 63–73. Google Scholar

116.

G. Hernández , C.G. Proud , T. Preiss , and A. Parsyan ( 2012). On the Diversification of the Translation Apparatus across Eukaryotes. Comp. Fund. Genomics 2012, 256848. Google Scholar

117.

J.W. Hershey , N. Sonenberg , and M.B. Mathews ( 2012). Principles of translational control: an overview. Cold Spring Harb. Perspect. Biol. 4, 1–10. Google Scholar

118.

C. Heufler , K.S. Browning , and J.M. Ravel ( 1988). Properties of the subunits of wheat germ initiation factor 3. Biochim. Biophys. Acta. 951, 182–190. Google Scholar

119.

H.J. Hiddinga , C.J. Crum , J. Hu , and D.A. Roth ( 1988). Viroid-induced phosphorylation of a host protein related to a dsRNA-dependent protein kinase. Science 241, 451–453. Google Scholar

120.

M. Hilbert , F. Kebbel , A. Gubaev , and D. Klostermeier ( 2011). eIF4G stimulates the activity of the DEAD box protein eIF4A by a conformational guidance mechanism. Nucl. Acids Res. 39, 2260–2270. Google Scholar

121.

A.G. Hinnebusch ( 2005). Translational regulation of GCN4 and the general amino acid control of yeast. Annu. Rev. Microbiol. 59, 407–450. Google Scholar

122.

A.G. Hinnebusch ( 2011). Molecular mechanism of scanning and start codon selection in eukaryotes. Microbiol. Mol. Biol. Rev. 75, 434–467. Google Scholar

123.

A.G. Hinnebusch ( 2014). The scanning mechanism of eukaryotic translation initiation. Annu. Rev. Biochem. 83, 779–812. Google Scholar

124.

A.G. Hinnebusch , and J.R. Lorsch ( 2012). The mechanism of eukaryotic translation initiation: New insights and challenges. Cold Spring Harb. Perspect. Biol. 4, 29–54. Google Scholar

125.

A.G. Hinnebusch , T.E. Dever , and K. Asano (2007). Mechanism of translation initiation in the yeast Saccharomyces cerevisiae. In Translational Control in Biology and Medicine, M.B. Mathews , N. Sonenberg , and J.W.B. Hershey , eds (Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press), pp. 225–268. Google Scholar

126.

A.A. Hizli , Y. Chi , J. Swanger , J.H. Carter , Y. Liao , M. Welcker , A.G. Ryazanov , and B.E. Clurman ( 2013). Phosphorylation of eukaryotic elongation factor 2 (eEF2) by cyclin A-cyclin-dependent kinase 2 regulates its inhibition by eEF2 kinase. Mol. Cell Biol. 33, 596–604. Google Scholar

127.

M.T. Hopkins , Y. Lampi , T.W. Wang , Z. Liu , and J.E. Thompson ( 2008). Eukaryotic translation initiation factor 5A is involved in pathogen-induced cell death and development of disease symptoms in Arabidopsis. Plant Physiol. 148, 479–489. Google Scholar

128.

G. Horiguchi , M. Van Lijsebettens , H. Candela , J.L. Micol , and H. Tsukaya ( 2012). Ribosomes and translation in plant developmental control. Plant Sci 191–192, 24–34. Google Scholar

129.

Y.F. Hsu , Y.C. Chen , Y.C. Hsiao , B.J. Wang , S.Y. Lin , W.H. Cheng , G.Y. Jauh , J.J. Harada , and C.S. Wang ( 2013). AtRH57, a DEAD-box RNA helicase, is involved in feedback inhibition of glucose-mediated abscisic acid accumulation during seedling development and additively affects pre-ribosomal RNA processing with high glucose. Plant J. 77, 119–135. Google Scholar

130.

V. Hugouvieux , J.M. Kwak , and J.I. Schroeder ( 2001). An mRNA cap binding protein, ABH1, modulates early abscisic acid signal transduction in Arabidopsis. Cell 106, 477–487. Google Scholar

131.

M. Hummel , J.H. Cordewener , J.C. de Groot , S. Smeekens , A.H. America , and J. Hanson ( 2012). Dynamic protein composition of Arabidopsis thaliana cytosolic ribosomes in response to sucrose feeding as revealed by label free MSE proteomics. Proteomics 12, 1024–1038. Google Scholar

132.

A.G. Hunt ( 2011). RNA regulatory elements and polyadenylation in plants. Front. Plant Sci. 2, 109. Google Scholar

133.

A.P. Hutchins , G.R. Roberts , C.W. Lloyd , and J.H. Doonan ( 2004). In vivo interaction between CDKAand eIF4A: a possible mechanism linking translation and cell proliferation. FEBS Lett. 556, 91–94. Google Scholar

134.

J. Hwang , C.S. Oh , and B.C. Kang ( 2013). Translation elongation factor 1B (eEF1B) is an essential host factor for tobacco mosaic virus infection in plants. Virology 439, 105–114. Google Scholar

135.

T.M. Immanuel , D.R. Greenwood , and R.M. MacDiarmid ( 2012). A critical review of translation initiation factor eIF2α kinases in plants-regulating protein synthesis during stress. Funct. Plant Biol. 39, 717–735. Google Scholar

136.

H.O. Iwakawa , Y. Tajima , T. Taniguchi , M. Kaido , K. Mise , Y. Tornari , H. Taniguchi , and T. Okuno ( 2012). Poly(A)-binding protein facilitates translation of an uncapped/nonpolyadenylated viral RNA by binding to the 3′ untranslated region. J. Virol. 86, 7836–7849. Google Scholar

137.

E. Izaurralde , J. Lewis , C. McGuigan , M. Jankowska , E. Darzynkiewicz , and I.W. Mattaj ( 1994). A nuclear cap binding protein complex involved in pre-mRNA splicing. Cell 78, 657–668. Google Scholar

138.

R.J. Jackson ( 2013). The current status of vertebrate cellular mRNA IRESs. Cold Spring Harb. Perspect. Biol. 5, a011569. Google Scholar

139.

R.J. Jackson , C.U. Hellen , and T.V. Pestova ( 2010). The mechanism of eukaryotic translation initiation and principles of its regulation. Nat. Rev. Mol. Cell Biol. 11, 113–127. Google Scholar

140.

R.J. Jackson , C.U. Hellen , and T.V. Pestova ( 2012). Termination and post-termination events in eukaryotic translation. Adv. Protein Chem. Struct. Biol. 86, 45–93. Google Scholar

141.

G. Jannot , S. Bajan , N.J. Giguère , S. Bouasker , I.H. Banville , S. Piquet , G. Hutvagner , and M.J. Simard ( 2011). The ribosomal protein RACK1 is required for microRNA function in both C. elegans and humans. EMBO Rep. 12, 581–586. Google Scholar

142.

H. Janska , and M. Kwasniak ( 2014). Mitoribosomal regulation of OXPHOS biogenesis in plants. Front. Plant Sci. 5, 79. Google Scholar

143.

M.D. Jennings , and G.D. Pavitt ( 2010). eIF5 is a dual function GAP and GDI for eukaryotic translational control. Small GTPases 1, 118–123. Google Scholar

144.

M.D. Jennings , Y. Zhou , S.S. Mohammad-Qureshi , D. Bennett , and G.D. Pavitt ( 2013). eIF2B promotes eIF5 dissociation from eIF2·GDP to facilitate guanine nucleotide exchange for translation initiation. Genes Dev. 27, 2696–2707. Google Scholar

145.

J. Jiang , and J.F. Laliberte ( 2011). The genome-linked protein VPg of plant viruses-a protein with many partners. Curr. Opin. Virol. 1, 347–354. Google Scholar

146.

J.R. Jiang , and S.D. Clouse ( 2001). Expression of a plant gene with sequence similarity to animal TGF-β receptor interacting protein is regulated by brassinosteroids and required for normal plant development. Plant J. 26, 35–45. Google Scholar

147.

Y. Jiao , J.L. Riechmann , and E.M. Meyerowitz ( 2008). Transcriptomewide analysis of uncapped mRNAs in Arabidopsis reveals regulation of mRNA degradation. Plant Cell 20, 2571–2585. Google Scholar

148.

S. Jiménez-López , E. Mancera-Martínez , A. Donayre-Torres , C. Rangel , L. Uribe , S. March , G. Jiménez-Sánchez , and E. Sánchez de Jiménez ( 2011). Expression profile of maize (Zea mays L.) embryonic axes during germination: translational regulation of ribosomal protein mRNAs. Plant Cell Physiol. 52, 1719–1733. Google Scholar

149.

R.A. Jorgensen , and A.E. Dorantes-Acosta ( 2012). Conserved peptide upstream open reading frames are associated with regulatory genes in angiosperms. Front. Plant Sci. 3, 191. Google Scholar

150.

B. Joshi , K. Lee , D.L. Maeder , and R. Jagus ( 2005). Phylogenetic analysis of eIF4E-family members. BMC Evol. Biol. 5, 48. Google Scholar

151.

P. Juntawong , and J. Bailey-Serres ( 2012). Dynamic Light Regulation of Translation Status in Arabidopsis thaliana. Front. Plant Sci. 3, 66. Google Scholar

152.

P. Juntawong , R. Sorenson , and J. Bailey-Serres ( 2013). Cold shock protein 1 chaperones mRNAs during translation in Arabidopsis thaliana. Plant J. 74, 1016–1028. Google Scholar

153.

P. Juntawong , T. Girke , J. Bazin , and J. Bailey-Serres ( 2014). Translational dynamics revealed by genome-wide profiling of ribosome foot-prints in Arabidopsis. Proc. Natl. Acad. Sci. USA 111, E203–212. Google Scholar

154.

M. Kalyna , C.G. Simpson , N.H. Syed , D. Lewandowska , Y. Marquez , B. Kusenda , J. Marshall , J. Fuller , L. Cardie , J. McNicol , H.Q. Dinh , A. Barta , and J.W. Brown ( 2012). Alternative splicing and nonsense-mediated decay modulate expression of important regulatory genes in Arabidopsis. Nucl. Acids Res. 40, 2454–2469. Google Scholar

155.

T. Kantidakis , B.A. Ramsbottom , J.L. Birch , S.N. Dowding , and R.J. White ( 2010). mTOR associates with TFIIIC, is found at tRNA and 5S rRNA genes, and targets their repressor Maf1. Proc. Natl. Acad. Sci. USA 107, 11823–11828. Google Scholar

156.

B. Karniol , A. Yahalom , S. Kwok , T. Tsuge , M. Matsui , X.W. Deng , and D.A. Chamovitz ( 1998). The Arabidopsis homologue of an eIF3 complex subunit associates with the COP9 complex. FEBS Lett. 439, 173–179. Google Scholar

157.

R. Kawaguchi , and J. Bailey-Serres ( 2002). Regulation of translational initiation in plants. Curr. Opin. Plant Biol. 5, 460–465. Google Scholar

158.

R. Kawaguchi , and J. Bailey-Serres ( 2005). mRNA sequence features that contribute to translational regulation in Arabidopsis. Nucl. Acids Res. 33, 955–965. Google Scholar

159.

R. Kawaguchi , T. Girke , E.A. Bray , and J. Bailey-Serres ( 2004). Differential mRNA translation contributes to gene regulation under non-stress and dehydration stress conditions in Arabidopsis thaliana. Plant J. 38, 823–839. Google Scholar

160.

Z. Kerényi , Z. Mérai , L. Hiripi , A. Benkovics , P. Gyula , C. Lacomme , E. Barta , F. Nagy , and D. Silhavy ( 2008). Inter-kingdom conservation of mechanism of nonsense-mediated mRNA decay. EMBO J. 27, 1585–1595. Google Scholar

161.

M.A. Khan , and D.J. Goss ( 2005). Translation initiation factor (eIF)4B affects the rates of binding of the mRNA m7G cap analogue to wheat germ eIFiso4F and eIFiso4F·PABP. Biochemistry 44, 4510–4516. Google Scholar

162.

M.A. Khan , and D.J. Goss ( 2012). Poly(A)-binding protein increases the binding affinity and kinetic rates of interaction of viral protein linked to genome with translation initiation factors eIFiso4F and eIFiso4F·4B complex. Biochemistry 51, 1388–1395. Google Scholar

163.

M.A. Khan , H. Yumak , and D.J. Goss ( 2009). Kinetic mechanism for the binding of eIF4F and tobacco etch virus internal ribosome entry site RNA: effects of eIF4B and poly(A)-binding protein. J. Biol. Chem. 284, 35461–35470. Google Scholar

164.

M.A. Khan , H. Yumak , D.R. Gallie , and D.J. Goss ( 2008). Effects of poly(A)-binding protein on the interactions of translation initiation factor eIF4F and eIF4F·4B with internal ribosome entry site (IRES) of tobacco etch virus RNA. Biochim. Biophys. Acta. 1779, 622–627. Google Scholar

165.

D. Khandal , I. Samol , F. Buhr , S. Pollmann , H. Schmidt , S. Clemens , S. Reinbothe , and C. Reinbothe ( 2009). Singlet oxygen-dependent translational control in the tigrina-d. 12 mutant of barley. Proc. Natl. Acad. Sci. USA 106, 13112–13117. Google Scholar

166.

S. Khoshnevis , F. Hauer , P. Milón , H. Stark , and R. Ficner ( 2012). Novel insights into the architecture and protein interaction network of yeast eIF3. RNA 18, 2306–2319. Google Scholar

167.

B.H. Kim , X. Cai , J.N. Vaughn , and A.G. Von Arnim ( 2007). On the functions of the h subunit of eukaryotic initiation factor 3 in late stages of translation initiation. Genome Biol. 8, R60. Google Scholar

168.

J. Kim , W.H. Kang , J. Hwang , H.B. Yang , K. Dosun , C.S. Oh , and B.C. Kang ( 2014a). Transgenic Brassica rapa plants over-expressing eIF(iso)4E variants show broad-spectrum Turnip mosaic virus (TuMV) resistance. Mol. Plant Pathol. 15, 615–626. Google Scholar

169.

T. Kim , K. Hofmann , A.G. von Arnim , and D.A. Chamovitz ( 2001). PCI complexes: pretty complex interactions in diverse signaling pathways. Trends Plant Sci. 6, 379–386. Google Scholar

170.

T.H. Kim , B.H. Kim , A. Yahalom , D.A. Chamovitz , and A.G. Von Arnim ( 2004). Translational regulation via 5′ mRNA leader sequences revealed by mutational analysis of the Arabidopsis translation initiation factor subunit eIF3h. Plant Cell 16, 3341–3356. Google Scholar

171.

Y. Kim , G. Lee , E. Jeon , E.J. Sohn , Y. Lee , H. Kang , D.W. Lee , D.H. Kim , and I. Hwang ( 2014b). The immediate upstream region of the 5′-UTR from the AUG start codon has a pronounced effect on the translational efficiency in Arabidopsis thaliana. Nucl. Acids Res. 42, 485–498. Google Scholar

172.

Y.K. Kim , S. Kim , Y.J. Shin , Y.S. Hur , W.Y. Kim , M.S. Lee , C.I. Cheon , and D.P. Verma ( 2014c). Ribo so mal protein S6, a target of rapamycin, is involved in the regulation of rRNA genes by possible epigenetic changes in Arabidopsis. J. Biol. Chem. 289, 3901–3912. Google Scholar

173.

S. Klinge , F. Voigts-Hoffmann , M. Leibundgut , and N. Ban ( 2012). Atomic structures of the eukaryotic ribosome. Trends Biochem. Sci. 37, 189–198. Google Scholar

174.

S.E. Kolitz , and J.R. Lorsch ( 2010). Eukaryotic initiator tRNA: finely tuned and ready for action. FEBS Lett. 584, 396–404. Google Scholar

175.

A.A. Komar , B. Mazumder , and W.C. Merrick ( 2012). A new framework for understanding IRES-mediated translation. Gene 502, 75–86. Google Scholar

176.

C. Koncz , F. Dejong , N. Villacorta , D. Szakonyi , and Z. Koncz ( 2012). The spliceosome-activating complex: molecular mechanisms underlying the function of a pleiotropic regulator. Front. Plant Sci. 3, 9. Google Scholar

177.

O.A. Koroleva , J.W. Brown , and P.J. Shaw ( 2009a). Localization of eIF4A-III in the nucleolus and splicing speckles is an indicator of plant stress. Plant Signal. Behav. 4, 1148–1151. Google Scholar

178.

O.A. Koroleva , G. Calder , A.F. Pendle , S.H. Kim , D. Lewandowska , C.G. Simpson , I.M. Jones , J.W. Brown , and P.J. Shaw ( 2009b). Dynamic behavior of Arabidopsis eIF4A-III, putative core protein of exon junction complex: fast relocation to nucleolus and splicing speckles under hypoxia. Plant Cell 21, 1592–1606. Google Scholar

179.

E. Kougioumoutzi , M. Cartolano , C. Canales , M. Dupré , J. Bramsiepe , D. Vlad , M. Rast , R. Dello Ioio , A. Tattersall , A. Schnittger , A. Hay , and M. Tsiantis ( 2013). SIMPLE LEAF3 encodes a ribosome-associated protein required for leaflet development in Cardamine hirsuta. Plant J. 73, 533–545. Google Scholar

180.

M. Kozak ( 1978). How do eucaryotic ribosomes select initiation regions in messenger RNA? Cell 15, 1109–1123. Google Scholar

181.

M. Kozak ( 1980). Evaluation of the “scanning model” for initiation of protein synthesis in eucaryotes. Cell 22, 7–8. Google Scholar

182.

M. Kozak ( 1986). Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell 44, 283–292. Google Scholar

183.

A. Kropiwnicka , K. Kuchta , M. Lukaszewicz , J. Kowalska , J. Jemielity , K. Ginalski , E. Darzynkiewicz , and J. Zuberek ( 2015). Five eIF4E isoforms from Arabidopsis thaliana are characterized by distinct features of cap analogs binding. Biochem. Biophys. Res. Commun. 456, 47–52. Google Scholar

184.

S. Lageix , E. Lanet , M.N. Pouch-Pelissier , M.C. Espagnol , C. Robaglia , J.M. Deragon , and T. Pelissier ( 2008). Arabidopsis eIF2α kinase GCN2 is essential for growth in stress conditions and is activated by wounding. BMC. Plant Biol. 8, 134. Google Scholar

185.

P. Lan , and W. Schmidt ( 2011). The enigma of eIF5A in the iron deficiency response of Arabidopsis. Plant Signal. Behav. 6, 528–530. Google Scholar

186.

J.O. Langland , S. Jin , B.L. Jacobs , and D.A. Roth ( 1995). Identification of a plant-encoded analog of PKR, the mammalian double-stranded RNA-dependent protein kinase. Plant Physiol. 108, 1259–1267. Google Scholar

187.

J.O. Langland , L.A. Langland , K.S. Browning , and D.A. Roth ( 1996). Phosphorylation of plant eukaryotic initiation factor-2 by the plant-encoded double-stranded RNA-dependent protein kinase, pPKR, and inhibition of protein synthesis in vitro. J. Biol. Chem. 271, 4539–4544. Google Scholar

188.

R. Latha , G.H. Salekdeh , J. Bennett , and M.S. Swaminathan ( 2004). Molecular analysis of a stress-induced cDNA encoding the translation initiation factor, eIF1, from the salt-tolerant wild relative of rice, Porteresia coarctata. Funct. Plant Biol. 31, 1035–1042. Google Scholar

189.

S.J. Lauer , K.S. Browning , and J.M. Ravel ( 1985). Characterization of initiation factor 3 from wheat germ. 2. Effects of polyclonal and monoclonal antibodies on activity. Biochemistry 24, 2928–2931. Google Scholar

190.

S.J. Lauer , E. Burks , J.D. Irvin , and J.M. Ravel ( 1984). Purification and characterization of three elongation factors, EF-1α, EF-1βy and EF-2, from wheat germ. J. Biol. Chem. 259, 1644–1648. Google Scholar

191.

S.R. Lax , J.J. Osterhout , and J.M. Ravel ( 1982). Factors from wheat germ that enhance the activity of eukaryotic initiation factor eIF-2: Isolation and characterization of Co-eIF2β. J. Biol. Chem. 257, 8233–8237. Google Scholar

192.

S.R. Lax , K.S. Browning , D.M. Maia , and J.M. Ravel ( 1986). ATPase Activities of Wheat Germ Initiation Factors 4A, 4B and 4F. J. Biol. Chem. 261, 15632–15636. Google Scholar

193.

E. Layat , J. Sáez-Vásquez , and S. Tourmente ( 2012). Regulation of Pol I-transcribed 45S rDNA and Pol III-transcribed 5S rDNA in Arabidopsis. Plant Cell Physiol. 53, 267–276. Google Scholar

194.

H. Le , and D.R. Gallie ( 2000). Sequence diversity and conservation of the poly(A)-binding protein in plants. Plant Sci. 152, 101–114. Google Scholar

195.

H. Le , K.S. Browning , and D.R. Gallie ( 2000). The phosphorylation state of poly(A)-binding protein specifies its binding to poly(A) RNA and its interaction with eukaryotic initiation factor (eIF) 4F, eIFiso4F, and eIF4B. J. Biol. Chem. 275, 17452–17462. Google Scholar

196.

H. Le , R.L. Tanguay , M.L. Balasta , C.C. Wei , K.S. Browning , A.M. Metz , D.J. Goss , and D.R. Gallie ( 1997). Translation initiation factors eIF-iso4G and eIF-4B interact with the poly(A)-binding protein and increase its RNA binding activity. J. Biol. Chem. 272, 16247–16255. Google Scholar

197.

F. Le Sourd , S. Boulben , R. Le Bouffant , P. Cormier , J. Morales , R. Belle , and O. Mulner-Lorillon ( 2006). eEF1B: At the dawn of the 21st century. Biochim. Biophys. Acta. 1759, 13–31. Google Scholar

198.

A.D. Lellis , M.L. Allen , A.W. Aertker , J.K. Tran , D.M. Hillis , C.R. Harbin , C. Caldwell , D.R. Gallie , and K.S. Browning ( 2010). Deletion of the eIFiso4G subunit of the Arabidopsis eIFiso4F translation initiation complex impairs health and viability. Plant Mol. Biol. 74, 249–263. Google Scholar

199.

G. Leprivier , M. Remke , B. Rotblat , A. Dubuc , A.R. Mateo , M. Kool , S. Agnihotri , A. El-Naggar , B. Yu , S.P. Somasekharan , B. Faubert , G. Bridon , C.E. Tognon , J. Mathers , R. Thomas , A. Li , A. Barokas , B. Kwok , M. Bowden , S. Smith , X. Wu , A. Korshunov , T. Hielscher , P.A. Northcott , J.D. Galpin , C.A. Ahern , Y. Wang , M.G. McCabe , V.P. Collins , R.G. Jones , M. Pollak , O. Delattre , M.E. Gleave , E. Jan , S.M. Pfister , C.G. Proud , W.B. Derry , M.D. Taylor , and P.H. Sorensen ( 2013). The eEF2 kinase confers resistance to nutrient deprivation by blocking translation elongation. Cell 153, 1064–1079. Google Scholar

200.

N. Leviatan , N. Alkan , D. Leshkowitz , and R. Fluhr ( 2013). Genomewide survey of cold stress regulated alternative splicing in Arabidopsis thaiiana with tiling microarray. PLoS One 8, e66511. Google Scholar

201.

M.W. Li , W.K. AuYeung , and H.M. Lam ( 2013a). The GCN2 homologue in Arabidopsis thaiiana interacts with uncharged tRNA and uses Arabidopsis eIF2α molecules as direct substrates. Plant Biol. 15, 13–18. Google Scholar

202.

P. Li , L. Ponnala , N. Gandotra , L. Wang , Y. Si , S.L. Tausta , T.H. Kebrom , N. Provart , R. Patel , C.R. Myers , E.J. Reidel , R. Turgeon , P. Liu , Q. Sun , T. Nelson , and T.P. Brutneil ( 2010). The developmental dynamics of the maize leaf transcriptome. Nat. Genet. 42, 1060–1067. Google Scholar

203.

S. Li , L. Liu , X. Zhuang , Y. Yu , X. Liu , X. Cui , L. Ji , Z. Pan , X. Cao , B. Mo , F. Zhang , N. Raikhel , L. Jiang , and X. Chen ( 2013b). MicroRNAs inhibit the translation of target mRNAs on the endoplasmic reticulum in Arabidopsis. Cell 153, 562–574. Google Scholar

204.

X.P. Li , P.C. Kahn , J.N. Kahn , P. Grela , and N.E. Tumer ( 2013c). Arginine residues on the opposite side of the active site stimulate the catalysis of ribosome depurination by ricin A chain by interacting with the P-protein stalk. J. Biol. Chem. 288, 30270–30284. Google Scholar

205.

Y. Li , and M. Kiledjian ( 2010). Regulation of mRNA decapping. Wiley Interdiscip. Rev. RNA 1, 253–265. Google Scholar

206.

Z. Li , and P.D. Nagy ( 2011). Diverse roles of host RNA binding proteins in RNA virus replication. RNA. Biol. 8, 305–315. Google Scholar

207.

Z. Li , J. Pogany , T. Panavas , K. Xu , A.M. Esposito , T.G. Kinzy , and P.D. Nagy ( 2009). Translation elongation factor 1A is a component of the tombusvirus replicase complex and affects the stability of the p33 replication co-factor. Virology 385, 245–260. Google Scholar

208.

P. Linder , and F. Fuller-Pace ( 2013). Looking back on the birth of DEAD-box RNA helicases. Biochim. Biophys. Acta. 1829, 750–755. Google Scholar

209.

M.J. Liu , S.H. Wu , J.F. Wu , W.D. Lin , Y.C. Wu , T.Y. Tsai , and H.L. Tsai ( 2013). Translational landscape of photomorphogenic Arabidopsis. Plant Cell 25, 3699–3710. Google Scholar

210.

Y. Liu , P. Neumann , B. Kuhle , T. Monecke , S. Schell , A. Chari , and R. Ficner ( 2014). Translation initiation factor eIF3b contains a ninebladed β-propeller and interacts with the 40S ribosomal subunit. Structure 22, 923–930. Google Scholar

211.

I.B. Lomakin , and T.A. Steitz ( 2013). The initiation of mammalian protein synthesis and mRNA scanning mechanism. Nature 500, 307–311. Google Scholar

212.

J.A. Lopez-Valenzuela , B.C. Gibbon , D.R. Holding , and B.A. Larkins ( 2004). Cytoskeletal proteins are coordinately increased in maize genotypes with high levels of eEF1A. Plant Physiol. 135, 1784–1797. Google Scholar

213.

J.A. Lopez-Valenzuela , B.C. Gibbon , P.A. Hughes , T.W. Dreher , and B.A. Larkins ( 2003). eEF1A isoforms change in abundance and actinbinding activity during maize endosperm development. Plant Physiol. 133, 1285–1295. Google Scholar

214.

J.R. Lorsch , and T.E. Dever ( 2010). Molecular view of 43S complex formation and start site selection in eukaryotic translation initiation. J. Biol. Chem. 285, 21203–21207. Google Scholar

215.

Y.J. Luo , and D.J. Goss ( 2001). Homeostasis in mRNA Initiation - Wheat germ poly(A)-binding protein lowers the activation energy barrier to Initiation complex formation. J. Biol. Chem. 276, 43083–43086. Google Scholar

216.

Y. Ma , E. Miura , B.K. Ham , H.W. Cheng , Y.J. Lee , and W.J. Lucas ( 2010). Pumpkin eIF5A isoforms interact with components of the translational machinery in the cucurbit sieve tube system. Plant J. 64, 536–550. Google Scholar

217.

L.D. Maldonado-Bonilla ( 2014). Composition and function of P bodies in Arabidopsis thaiiana. Front. Plant Sci. 5, 201. Google Scholar

218.

A. Marintchev ( 2013). Roles of helicases in translation Initiation: A mechanistic view. Biochim. Biophys. Acta. 1829, 799–809. Google Scholar

219.

A. Marintchev , and G. Wagner ( 2005). eIF4G and CBP80 share a common origin and similar domain organization: implications for the structure and function of eIF4G. Biochemistry 44, 12265–12272. Google Scholar

220.

A. Marintchev , K.A. Edmonds , B. Marintcheva , E. Hendrickson , M. Oberer , C. Suzuki , B. Herdy , N. Sonenberg , and G. Wagner ( 2009). Topology and regulation of the human eIF4A/4G/4H helicase complex in translation initiation. Cell 136, 447–460. Google Scholar

221.

Y. Marquez , J.W. Brown , C. Simpson , A. Barta , and M. Kalyna ( 2012). Transcriptome survey reveals increased complexity of the alternative splicing landscape in Arabidopsis. Genome Res 22, 1184–1195. Google Scholar

222.

P. Martin-Marcos , J.S. Nanda , R.E. Luna , F. Zhang , A.K. Saini , V.A. Cherkasova , G. Wagner , J.R. Lorsch , and A.G. Hinnebusch ( 2014). Enhanced eIF1 binding to the 40S ribosome impedes conformational rearrangements of the preinitiation complex and elevates Initiation accuracy. RNA 20, 150–167. Google Scholar

223.

D. Matsuda , S. Yoshinari , and T.W. Dreher ( 2004). eEF1 A binding to aminoacylated viral RNA represses minus strand synthesis by TYMV RNA-dependent RNA polymerase. Virology 321, 47–56. Google Scholar

224.

L.K. Mayberry , M.L. Allen , M.D. Dennis , and K.S. Browning ( 2009). Evidence for variation in the optimal translation initiation complex: plant eIF4B, eIF4F, and eIF(iso)4F differentially promote translation of mRNAs. Plant Physiol. 150, 1844–1854. Google Scholar

225.

L.K. Mayberry , M.L. Allen , K.R. Nitka , L. Campbell , P.A. Murphy , and K.S. Browning ( 2011). Plant cap-binding complexes eukaryotic initiation factors eIF4F and eIFiso4F: Molecular specificity of subunit binding. J. Biol. Chem. 286, 42566–42574. Google Scholar

226.

K.B. McIntosh , and P.C. Bonham-Smith ( 2006). Ribosomal protein gene regulation: what about plants? Can. J. Bot. 84, 342–362. Google Scholar

227.

E.J. Mead , R.J. Masterton , T. von der Haar , M.F. Tuite , and C.M. Smales ( 2014). Control and regulation of mRNA translation. Blochem. Soc. Trans. 42, 151–154. Google Scholar

228.

H. Meng , C. Li , Y. Wang , and G. Chen ( 2014). Molecular dynamics simulation of the allosteric regulation of eIF4A protein from the open to closed state, induced by ATP and RNA substrates. PLoS One 9, e86104. Google Scholar

229.

W.C. Merrick , and M.E. Harris ( 2014). Control not at initiation? Bah, humbug! EMBO J. 33, 3–4. Google Scholar

230.

A.M. Metz , and K.S. Browning ( 1997). Assignment of the β-subunit of wheat eIF2 by protein and DNA sequence analysis and immunoanalysis. Arch. Biochem. Biophys. 342, 187–189. Google Scholar

231.

A.L. Milac , E. Bojarska , and A. Wypijewska Del Nogal ( 2014). Decapping scavenger (DcpS) enzyme: Advances in its structure, activity and roles in the cap-dependent mRNA metabolism. Biochim. Biophys. Acta. 839, 452–462. Google Scholar

232.

A. Miluzio , A. Beugnet , V. Volta , and S. Biffo ( 2009). Eukaryotic initiation factor 6 mediates a continuum between 60S ribosome biogenesis and translation. EMBO Rep. 10, 459–465. Google Scholar

233.

A.F. Monzingo , S. Dhaliwal , A. Dutt-Chaudhuri , A. Lyon , J.H. Sadow , D.W. Hoffman , J.D. Robertus , and K.S. Browning ( 2007). The structure of eukaryotic translation initiation factor-4E from wheat reveals a novel disulfide bond. Plant Physiol. 143, 1504–1518. Google Scholar

234.

M. Morita , L.W. Ler , M.R. Fabian , N. Siddiqui , M. Mullin , V.C. Henderson , T. Alain , B.D. Fonseca , G. Karashchuk , C.F. Bennett , T. Kabuta , S. Higashi , O. Larsson , I. Topisirovic , R.J. Smith , A.C. Gingras , and N. Sonenberg ( 2012). Anovel 4EHP-GIGYF2 translational repressor complex is essential for mammalian development. Mol. Cell Biol. 32, 3585–3593. Google Scholar

235.

B. Moury , C. Charron , B. Janzac , V. Simon , J.L. Gallois , A. Palloix , and C. Garanta ( 2013). Evolution of plant eukaryotic initiation factor 4E (eIF4E) and potyvirus genome-linked protein (VPg): A game of mirrors impacting resistance spectrum and durability. Infect. Genet. Evol. 27, 472–480. Google Scholar

236.

D.G. Muench , C. Zhang , and M. Dahodwala ( 2012). Control of cytoplasmic translation in plants. Wiley Interdiscip. Rev. RNA 3, 178–194. Google Scholar

237.

J.J. Mulekar , and E. Huq ( 2013). Expanding roles of protein kinase CK2 in regulating plant growth and development. J. Exp. Bot. 65, 2883–2893. Google Scholar

238.

A. Mustroph , M.E. Zanetti , C.J. Jang , H.E. Holtan , P.P. Repetti , D.W. Galbraith , T. Girke , and J. Bailey-Serres ( 2009). Profiling translate mes of discrete cell populations resolves altered cellular priorities during hypoxia in Arabidopsis. Proc. Natl. Acad. Sci. USA 106, 18843–18848. Google Scholar

239.

A. Muñoz , and M.M. Castellano ( 2012). Regulation of translation initiation under abiotic stress conditions in plants: Is it a conserved or not so conserved process among eukaryotes? Comp. Funct. Genomics 2012, 406357. Google Scholar

240.

J.S. Nanda , A.K. Saini , A.M. Muñoz , A.G. Hinnebusch , and J.R. Lorsch ( 2013). Coordinated movements of eukaryotic translation initiation factors eIF1, eIF1A, and eIF5 trigger phosphate release from eIF2 in response to start codon recognition by the ribosomal preinitiation complex. J. Biol. Chem. 288, 5316–5329. Google Scholar

241.

J.S. Nanda , Y.N. Cheung , J.E. Takacs , P. Martin-Marcos , A.K. Saini , A.G. Hinnebusch , and J.R. Lorsch ( 2009). eIF1 controls multiple steps in start codon recognition during eukaryotic translation initiation. J. Mol. Biol. 394, 268–285. Google Scholar

242.

M. Nicolaï , M.A. Roncato , A.S. Canoy , D. Rouquié , X. Sarda , G. Freyssinet , and C. Robaglia ( 2006). Large-scale analysis of mRNA translation states during sucrose starvation in Arabidopsis cells identifies cell proliferation and chromatin structure as targets of translational control. Plant Physiol. 141, 663–673. Google Scholar

243.

T. Nishimura , T. Wada , K.T. Yamamoto , and K. Okada ( 2005). The Arabidopsis STV1 protein, responsible for translation reinitiation, is required for auxin-mediated gynoecium patterning. Plant Cell 17, 2940–2953. Google Scholar

244.

J.P. O'Brien , L.K. Mayberry , P.A. Murphy , K.S. Browning , and J.S. Brodbelt ( 2013). Evaluating the conformation and binding interface of cap-binding proteins and complexes via ultraviolet photodissociation mass spectrometry. J. Proteo me Res. 12, 5867–5877. Google Scholar

245.

P.A. Ortiz , R. Ulloque , G.K. Kihara , H. Zheng , and T.G. Kinzy ( 2006). Translation elongation factor 2 anticodon mimicry domain mutants affect fidelity and diphtheria toxin resistance. J. Biol. Chem. 281, 32639–32648. Google Scholar

246.

J.J. Osterhout , S.R. Lax , and J.M. Ravel ( 1983). Factors from wheat germ that enhance the activity of eukaryotic initiation factor eIF-2: Isolation and characterization of Co-eIF-2α. J. Biol. Chem. 258, 8285–8289. Google Scholar

247.

S.K. Pal , M. Liput , M. Piques , H. Ishihara , T. Obata , M.C. Martins , R. Sulpice , J.T. van Dongen , A.R. Fernie , U.P. Yadav , J.E. Lunn , B. Usadel , and M. Stitt ( 2013). Diurnal changes of polysome loading track sucrose content in the rosette of wild-type Arabidopsis and the starchless pgm mutant. Plant Physiol. 162, 1246–1265. Google Scholar

248.

I. Papp , L.A. Mur , A. Dalmadi , S. Dulai , and C. Koncz ( 2004). A mutation in the cap binding protein 20 gene confers drought tolerance to Arabidopsis. Plant Mol. Biol. 55, 679–686. Google Scholar

249.

E.H. Park , S.E. Walker , J.M. Lee , S. Rothenburg , J.R. Lorsch , and A.G. Hinnebusch ( 2011). Multiple elements in the eIF4G1 N-terminus promote assembly of eIF4G1·PABP mRNPs in vivo. EMBO J. 30, 302–316. Google Scholar

250.

E.H. Park , S.E. Walker , F. Zhou , J.M. Lee , V. Rajagopal , J.R. Lorsch , and A.G. Hinnebusch ( 2012). Yeast eukaryotic initiation factor (eIF) 4B enhances complex assembly between eIF4A and eIF4G in vivo. J. Biol. Chem. 288, 2340–2354. Google Scholar

251.

H.S. Park , K.S. Browning , T. Hohn , and L.A. Ryabova ( 2004). Eucaryotic initiation factor 4B controls eIF3-mediated ribosomal entry of viral reinitiation factor. EMBO J. 23, 1381–1391. Google Scholar

252.

H.S. Park , A. Himmelbach , K.S. Browning , T. Hohn , and L.A. Ryabova ( 2001). A plant viral “reinitiation” factor interacts with the host translational machinery. Cell 106, 723–733. Google Scholar

253.

A. Parsyan , Y. Svitkin , D. Shahbazian , C. Gkogkas , P. Lasko , W.C. Merrick , and N. Sonenberg ( 2011). mRNA helicases: the tacticians of translational control. Nat. Rev. Mol. Cell Biol. 12, 235–245. Google Scholar

254.

R.M. Patrick , and K.S. Browning ( 2012). The eIF4F and eIFiso4F complexes of plants: An evolutionary perspective. Comp Funct. Genomics 2012, 287814. Google Scholar

255.

R.M. Patrick , L.K. Mayberry , G. Choy , L.E. Woodard , J.S. Liu , A. White , R.A. Mullen , T.M. Tanavin , C.A. Latz , and K.S. Browning ( 2014). Two Arabidopsis loci encode novel eukaryotic initiation factor 4E isoforms that are functionally distinct from the conserved plant eukaryotic initiation factor 4E. Plant Physiol. 164, 1820–1830. Google Scholar

256.

T. Paz-Aviram , A. Yahalom , and D.A. Chamovitz ( 2008). Arabidopsis eIF3e interacts with subunits of the ribosome, Cop9 signalosome and proteasome. Plant Signal. Behav. 3, 409–411. Google Scholar

257.

K.A. Petsch , J. Mylne , and J.R. Botella ( 2005). Cosuppression of eukaryotic release factor 1-1 in Arabidopsis affects cell elongation and radial cell division. Plant Physiol. 139, 115–126. Google Scholar

258.

E. Pick , K. Hofmann , and M.H. Glickman ( 2009). PCI complexes: Beyond the proteasome, CSN, and eIF3 troika. Mol. Cell 35, 260–264. Google Scholar

259.

M. Piques , W.X. Schulze , M. Höhne , B. Usadel , Y. Gibon , J. Rohwer , and M. Stitt ( 2009). Ribosome and transcript copy numbers, polysome occupancy and enzyme dynamics in Arabidopsis. Mol. Syst. Biol. 5, 314. Google Scholar

260.

A.V. Pisarev , C.U. Hellen , and T.V. Pestova ( 2007). Recycling of eukaryotic posttermination ribosomal complexes. Cell 131, 286–299. Google Scholar

261.

A.V. Pisarev , M.A. Skabkin , V.P. Pisareva , O.V. Skabkina , A.M. Rakotondrafara , M.W. Hentze , C.U. Hellen , and T.V. Pestova ( 2010). The role of ABCE1 in eukaryotic posttermination ribosomal recycling. Mol. Cell 37, 196–210. Google Scholar

262.

V.P. Pisareva , and A.V. Pisarev ( 2014). eIF5 and eIF5B together stimulate 48S initiation complex formation during ribosomal scanning. Nucl. Acids Res. 42, 12052–12069. Google Scholar

263.

A. Preis , A. Heuer , C. Barrio-García , A. Hauser , D.E. Eyler , O. Berninghausen , R. Green , T. Becker , and R. Beckmann ( 2014). Cryoelectron microscopic structures of eukaryotic translation termination complexes containing eRF1·eRF3 or eRF1·ABCE1. Cell Rep. 8, 59–65. Google Scholar

264.

A.A. Putnam , and E. Jankowsky ( 2013). DEAD-box helicases as integrators of RNA, nucleotide and protein binding. Biochim. Biophys. Acta. 1829, 884–893. Google Scholar

265.

E.T. Pyl , M. Piques , A. Ivakov , W. Schulze , H. Ishihara , M. Stitt , and R. Sulpice ( 2012). Metabolism and growth in Arabidopsis depend on the daytime temperature but are temperature-compensated against cool nights. Plant Cell 24, 2443–2469. Google Scholar

266.

J. Querol-Audi , C. Sun , J.M. Vogan , M.D. Smith , Y. Gu , J.H. Cate , and E. Nogales ( 2013). Architecture of human translation initiation factor 3. Structure 21, 920–928. Google Scholar

267.

K.D. Raczynska , A. Stepien , D. Kierzkowski , M. Kalak , M. Bajczyk , J. McNicol , C.G. Simpson , Z. Szweykowska-Kulinska , J.W. Brown , and A. Jarmolowski ( 2014). The SERRATE protein is involved in alternative splicing in Arabidopsis thaliana. Nucleic Acids Res 42, 1224–1244. Google Scholar

268.

F. Rahmani , M. Hummel , J. Schuurmans , A. Wiese-Klinkenberg , S. Smeekens , and J. Hanson ( 2009). Sucrose control of translation mediated by an upstream open reading frame-encoded peptide. Plant Physiol. 150, 1356–1367. Google Scholar

269.

S. Rasheedi , M. Suragani , S.K. Haq , R. Sachchidanand, Bhardwaj , S.E. Hasnain , and N.Z. Ehtesham ( 2010). Expression, purification and ligand binding properties of the recombinant translation initiation factor (PeIFSB) from Pisum sativum. Mol. Cell Biochem. 344, 33–41. Google Scholar

270.

A. Rausell , R. Kanhonou , L. Yenush , R. Serrano , and R. Ros ( 2003). The translation initiation factor eIF1 Ais an important determinant in the tolerance to NaCl stress in yeast and plants. Plant J. 34, 257–267. Google Scholar

271.

P. Raychaudhuri , E.A. Stringer , D.M. Valenzuela , and U. Maitra ( 1984). Ribosomal subunit antiassociation activity in rabbit reticulocyte lysates. Evidence for a low molecular weight ribosomal subunit antiassociation protein factor (Mr = 25,000). J. Biol. Chem. 259, 11930–11935. Google Scholar

272.

A.S. Reddy ( 2007). Alternative splicing of pre-messenger RNAs in plants in the genomic era. Annu. Rev. Plant. Biol. 58, 267–294. Google Scholar

273.

A.S. Reddy , Y. Marquez , M. Kalyna , and A. Barta ( 2013). Complexity of the alternative splicing landscape in plants. Plant Cell 25, 3657–3683. Google Scholar

274.

B. Ren , Q. Chen , S. Hong , W. Zhao , J. Feng , H. Feng , and J. Zuo ( 2013). The Arabidopsis eukaryotic translation initiation factor eIF5A-2 regulates root protoxylem development by modulating cytokinin signaling. Plant Cell 25, 3841–3857. Google Scholar

275.

M. Ren , S. Qiu , P. Venglat , D. Xiang , L. Feng , G. Selvaraj , and R. Datla ( 2011). Target of rapamycin regulates development and ribosomal RNA expression through kinase domain in Arabidopsis. Plant Physiol. 155, 1367–1382. Google Scholar

276.

M. Ren , P. Venglat , S. Qiu , L. Feng , Y. Cao , E. Wang , D. Xiang , J. Wang , D. Alexander , S. Chalivendra , D. Logan , A. Mattoo , G. Selvaraj , and R. Datla ( 2012). Target of rapamycin signaling regulates metabolism, growth, and life span in Arabidopsis. Plant Cell 24, 4850–4874. Google Scholar

277.

R.E. Rhoads ( 2009). eIF4E: new family members, new binding partners, new roles. J. Biol. Chem. 284, 16711–16715. Google Scholar

278.

J.D. Richter , and N. Sonenberg ( 2005). Regulation of cap-dependent translation by eIF4E inhibitory proteins. Nature 433, 477–480. Google Scholar

279.

J.L. Riechmann , T. Ito , and E.M. Meyerowitz ( 1999). Non-AUG initiation of AGAMOUS mRNA translation in Arabidopsis thaliana. Mol. Cell Biol. 19, 8505–8512. Google Scholar

280.

C. Robaglia , and C. Garanta ( 2006). Translation initiation factors: a weak link in plant RNA virus infection. Trends Plant Sci. 11, 40–45. Google Scholar

281.

C. Robaglia , M. Thomas , and C. Meyer ( 2012). Sensing nutrient and energy status by SnRK1 and TOR kinases. Curr. Opin. Plant Biol. 15, 301–307. Google Scholar

282.

G.W. Rogers Jr ., A.A. Komar , and W.C. Merrick ( 2002). eIF4A: The godfather of the DEAD box helicases. Prog. Nucl. Acid Res. Mol. Biol. 72, 307–331. Google Scholar

283.

K. Rogers , and X. Chen ( 2013). Biogenesis, turnover, and mode of action of plant microRNAs. Plant Cell 25, 2383–2399. Google Scholar

284.

E. Rom , H.C. Kim , A.C. Gingras , J. Marcotrigiano , D. Favre , H. Olsen , S.K. Burley , and N. Sonenberg ( 1998). Cloning and characterization of 4EHP, a novel mammalian eIF4E-related cap-binding protein. J. Biol. Chem. 273, 13104–13109. Google Scholar

285.

A. Rosado , and N.V. Raikhel ( 2010). Application of the gene dosage balance hypothesis to auxin-related ribosomal mutants in Arabidopsis. Plant Signal. Behav. 5, 450–452. Google Scholar

286.

A. Rosado , R. Li , W. van de Ven , E. Hsu , and N.V. Raikhel ( 2012). Arabidopsis ribosomal proteins control developmental programs through translational regulation of auxin response factors. Proc. Natl. Acad. Sci. USA 109, 19537–19544. Google Scholar

287.

B. Roy , and A.G. von Arnim ( 2013). Translational regulation of cytoplasmic mRNAs. The Arabidopsis Book 11, e0165. Google Scholar

288.

B. Roy , J.N. Vaughn , B.H. Kim , F. Zhou , M.A. Gilchrist , and A.G. Von Arnim ( 2010). The h subunit of eIF3 promotes reinitiation competence during translation of mRNAs harboring upstream open reading frames. RNA. 16, 748–761. Google Scholar

289.

D.W. Russell , and L.L. Spremulli ( 1978). Identification of a wheat germ ribosome dissociation factor distinct from initiation factor eIF-3. J. Biol. Chem. 253, 6647–6649. Google Scholar

290.

D.W. Russell , and L.L. Spremulli ( 1979). Purification and characterization of a ribosome dissociation factor (eukaryotic initiation factor 6) from wheat germ. J. Biol. Chem. 254, 8796–8800. Google Scholar

291.

D.W. Russell , and L.L. Spremulli ( 1980). Mechanism of action of the wheat germ ribosome dissociation factor: interaction with the 60 S subunit. Arch. Biochem. Biophys. 201, 518–526. Google Scholar

292.

K.A. Ruud , C. Kuhlow , D.J. Goss , and K.S. Browning ( 1998). Identification and characterization of a novel cap-binding protein from Arabidopsis thaliana. J. Biol. Chem. 273, 10325–10330. Google Scholar

293.

B. Safer ( 1989). Nomenclature of initiation, elongation and termination factors for translation in eukaryotes. Eur. J. Biochem. 186, 1–3. Google Scholar

294.

R.K. Sahoo , S.S. Gill , and N. Tuteja ( 2012). Pea DNA helicase 45 promotes salinity stress tolerance in IR64 rice with improved yield. Plant Signal. Behav. 7, 1042–1046. Google Scholar

295.

A.K. Saini , J.S. Nanda , P. Martin-Marcos , J. Dong , F. Zhang , M. Bhardwaj , J.R. Lorsch , and A.G. Hinnebusch ( 2014). Eukaryotic translation initiation factor eIF5 promotes the accuracy of start codon recognition by regulating Pi release and conformational transitions of the preinitiation complex. Nucl. Acids Res. 42, 9623–9640. Google Scholar

296.

A.N. Sasikumar , W.B. Perez , and T.G. Kinzy ( 2012). The many roles of the eukaryotic elongation factor 1 complex. Wiley Interdiscip. Rev. RNA. 3, 543–555. Google Scholar

297.

Z. Sasvari , L. Izotova , T.G. Kinzy , and P.D. Nagy ( 2011). Synergistic roles of eukaryotic translation elongation factors 1By and 1A in stimulation of tombusvirus minus-strand synthesis. PLoS Pathog. 7, e1002438. Google Scholar

298.

M. Schepetilnikov , M. Dimitrova , E. Mancera-Martinez , A. Geldreich , M. Keller , and L.A. Ryabova ( 2013). TOR and S6K1 promote translation reinitiation of uORF-containing mRNAs via phosphorylation of eIF3h. EMBO J. 32, 1087–1102. Google Scholar

299.

M. Schepetilnikov , K. Kobayashi , A. Geldreich , C. Garanta , C. Robaglia , M. Keller , and L.A. Ryabova ( 2011). Viral factor TAV recruits TOR/S6K1 signalling to activate reinitiation after long ORF translation. EMBO J. 30, 1343–1356. Google Scholar

300.

E. Schmitt , M. Naveau , and Y. Mechulam ( 2010). Eukaryotic and archaeal translation initiation factor 2: a heterotrimeric tRNA carrier. FEBS Lett. 584, 405–412. Google Scholar

301.

S. Schmollinger , T. Mühlhaus , N.R. Boyle , I.K. Blaby , D. Casero , T. Mettler , J.L. Moseley , J. Kropat , F. Sommer , D. Strenkert , D. Hemme , M. Pellegrini , A.R. Grossman , M. Stitt , M. Schroda , and S.S. Merchant ( 2014). Nitrogen-sparing mechanisms in Chlamydomonas affect the transcriptome, the proteome, and photosynthetic metabolism. Plant Cell 26, 1410–1435. Google Scholar

302.

P. Schütz , M. Bumann , A.E. Oberholzer , C. Bieniossek , H. Trachsel , M. Altmann , and U. Baumann ( 2008). Crystal structure of the yeast eIF4A-eIF4G complex: an RNA-helicase controlled by protein-protein interactions. Proc. Natl. Acad. Sci. USA 105, 9564–9569. Google Scholar

303.

S.N. Seal , A. Schmidt , and A. Marcus ( 1983). Wheat Germ eIF-2 and Co-eIF-2: Resolution and functional characterization in in vitro protein synthesis. J. Biol. Chem. 258, 10573–10576. Google Scholar

304.

S.M. Shaikhin , S.K. Smailov , A.V. Lee , E.V. Kozhanov , and B.K. Iskakov ( 1992). Interaction of wheat germ translation initiation factor 2 with GDP and GTP. Biochimie 74, 447–454. Google Scholar

305.

Y.J. Shin , S. Kim , H. Du , S. Choi , D.P. Verma , and C.I. Cheon ( 2012). Possible dual regulatory circuits involving AtS6K1 in the regulation of plant cell cycle and growth. Mol. Cells 33, 487–496. Google Scholar

306.

K. Si , J. Chaudhuri , J. Chevesich , and U. Maitra ( 1997). Molecular cloning and functional expression of a human cDNA encoding translation initiation factor 6. Proc. Natl. Acad. Sci. 94, 14285–14290. Google Scholar

307.

N. Siddiqui , M.J. Osborne , D.R. Gallie , and K. Gehring ( 2007). Solution structure of the PABC domain from wheat poly (A)-binding protein: An insight into RNA metabolic and translational control in plants. Biochemistry 46, 4221–4231. Google Scholar

308.

A.E. Simon , and W.A. Miller ( 2013). 3′ cap-independent translation enhancers of plant viruses. Annu. Rev. Microbiol. 67, 21–42. Google Scholar

309.

G.G. Simpson , R.E. Laurie , P.P. Dijkwel , V. Quesada , P.A. Stockwell , C. Dean , and R.C. Macknight ( 2010). Noncanonical translation initiation of the Arabidopsis flowering time and alternative polyadenylation regulator FCA. Plant Cell 22, 3764–3777. Google Scholar

310.

B. Singh , H. Chauhan , J.P. Khurana , P. Khurana , and P. Singh ( 2013). Evidence for the role of wheat eukaryotic translation initiation factor 3 subunit g (TaeIF3g) in abiotic stress tolerance. Gene 532, 177–185. Google Scholar

311.

C.R. Singh , R. Watanabe , W. Chowdhury , H. Hiraishi , M.J. Murai , Y. Yamamoto , D. Miles , Y. Ikeda , M. Asano , and K. Asano ( 2012). Sequential eukaryotic translation initiation factor 5 (eIF5) binding to the charged disordered segments of eIF4G and eIF2β stabilizes the 48S preinitiation complex and promotes its shift to the initiation mode. Mol. Cell Biol. 32, 3978–3989. Google Scholar

312.

G., M., J. Singh , R. Kulshreshtha , J.P. Khurana , S. Kumar , and P. Singh ( 2007). Expression analysis of genes encoding translation initiation factor 3 subunit g (TaeIF3g) and vesicle-associated membrane protein-associated protein (TaVAP) in drought tolerant and susceptible cultivare of wheat. Plant Sci. 173, 660–669. Google Scholar

313.

B. Siridechadilok , C.S. Fraser , R.J. Hall , J.A. Doudna , and E. Nogales ( 2005). Structural roles for human translation factor eIF3 in initiation of protein synthesis. Science 310, 1513–1515. Google Scholar

314.

M.A. Skabkin , O.V. Skabkina , C.U. Hellen , and T.V. Pestova ( 2013). Reinitiation and other unconventional posttermination events during eukaryotic translation. Mol. Cell 51, 249–264. Google Scholar

315.

S.K. Smailov , A.V. Lee , and B.K. Iskakov ( 1993). Study of phosphorylation of translation elongation factor 2 (EF-2) from wheat germ. FEBS Lett. 321, 219–223. Google Scholar

316.

R.W. Smith , and N.K. Gray ( 2010). Poly(A)-binding protein (PABP): a common viral target. Biochem J. 426, 1–12. Google Scholar

317.

M. Sokabe , C.S. Fraser , and J.W. Hershey ( 2012). The human translation initiation multi-factor complex promotes methionyl-tRNAi binding to the 40S ribosomal subunit. Nucl. Acids Res. 40, 905–913. Google Scholar

318.

N. Sonenberg , and A.G. Hinnebusch ( 2009). Regulation of translation initiation in eukaryotes: mechanisms and biological targets. Cell 136, 731–745. Google Scholar

319.

R. Sorenson , and J. Bailey-Serres ( 2014). Selective mRNA sequestration by OLIGOURIDYLATE-BINDING PROTEIN 1 contributes to translational control during hypoxia in Arabidopsis. Proc. Natl. Acad. Sci. USA 111, 2373–2378. Google Scholar

320.

R. Sormani , C. Masclaux-Daubresse , F. Daniel-Vedele , F. Daniele-Vedele , and F. Chardon ( 2011a). Transcriptional regulation of ribosome components are determined by stress according to cellular compartments in Arabidopsis thaliana. PLoS One 6, e28070. Google Scholar

321.

R. Sormani , E. Delannoy , S. Lageix , F. Bitton , E. Lanet , J. Saez-Vasquez , J.M. Deragon , J.P. Renou , and C. Robaglia ( 2011b). Sublethal cadmium intoxication In Arabidopsis thaliana impacts translation at multiple levels. Plant Cell Physiol. 52, 436–447. Google Scholar

322.

C. Speth , E.M. Willing , S. Rausch , K. Schneeberger , and S. Laubinger ( 2013). RACK1 scaffold proteins influence miRNA abundance in Arabidopsis. Plant J. 76, 433–445. Google Scholar

323.

D. Staiger , and J.W. Brown ( 2013). Alternative splicing at the intersection of biological timing, development, and stress responses. Plant Cell 25, 3640–3656. Google Scholar

324.

R. Sulpice , A. Flis , A.A. Ivakov , F. Apelt , N. Krohn , B. Encke , C. Abel , R. Feil , J.E. Lunn , and M. Stitt ( 2014). Arabidopsis coordinates the diurnal regulation of carbon allocation and growth across a wide range of photoperiods. Mol. Plant 7, 137–155. Google Scholar

325.

Y.L. Sun , and S.K. Hong ( 2013). Sensitivity of translation initiation factor eIF1 as a molecular target of salt toxicity to sodic-alkaline stress in the halophytic grass Leymus chinensis. Biochem. Genet. 51, 101–118. Google Scholar

326.

M. Suragani , S. Rasheedi , S.E. Hasnain , and N.Z. Ehtesham ( 2011). The translation initiation factor, PeIFSB, from Pisum sativum displays chaperone activity. Biochem. Biophys. Res. Commun. 414, 390–396. Google Scholar

327.

N.H. Syed , M. Kalyna , Y. Marquez , A. Barta , and J.W. Brown ( 2012). Alternative splicing in plants-coming of age. Trends Plant Sci. 17, 616–623. Google Scholar

328.

B. Szamecz , E. Rutkai , L. Cuchalová , V. Munzarová , A. Herrmannová , K.H. Nielsen , L. Burela , A.G. Hinnebusch , and L. Valásek ( 2008). eIF3a cooperates with sequences 5′ of uORF1 to promote resumption of scanning by post-termination ribosomes for reinitiation on GCN4 mRNA. Genes Dev. 22, 2414–2425. Google Scholar

329.

K. Szick , M. Springer , and J. Bailey-Serres ( 1998). Evolutionary analyses of the 12-kDa acidic ribosomal P-proteins reveal a distinct protein of higher plant ribosomes. Proc. Natl. Acad. Sci. USA 95, 2378–2383. Google Scholar

330.

K. Szick-Miranda , and J. Bailey-Serres ( 2001). Regulated heterogeneity in 12-kDa P-protein phosphorylation and composition of ribosomes in maize (Zea mays L.). J. Biol. Chem. 276, 10921–10928. Google Scholar

331.

M.M. Tajrishi , N. Vaid , R. Tuteja , and N. Tuteja ( 2011). Overexpression of a pea DNA helicase 45 in bacteria confers salinity stress tolerance. Plant Signal. Behav. 6, 1271–1275. Google Scholar

332.

J. Tcherkezian , M. Cargnello , Y. Romeo , E.L. Huttlin , G. Lavoie , S.P. Gygi , and P.P. Roux ( 2014). Proteomic analysis of cap-dependent translation identifies LARP1 as a key regulator of 5′TOP mRNA translation. Genes Dev. 28, 357–371. Google Scholar

333.

O. Thiebeauld , M. Schepetilnikov , H.S. Park , A. Geldreich , K. Kobayashi , M. Keller , T. Hohn , and L.A. Ryabova ( 2009). A new plant protein interacts with eIF3 and 60S to enhance virus-activated translation re-initiation. EMBO J. 28, 3171–3184. Google Scholar

334.

C.C. Thoreen , L. Chantranupong , H.R. Keys , T. Wang , N.S. Gray , and D.M. Sabatini ( 2012). A unifying model for mTORC1-mediated regulation of mRNA translation. Nature 485, 109–113. Google Scholar

335.

N. Tiller , and R. Bock ( 2014). The translational apparatus of plastids and its role in plant development. Mol. Plant 7, 1105–1120. Google Scholar

336.

R.T. Timmer , S.R. Lax , D.L. Hughes , W.C. Merrick , J.M. Ravel , and K.S. Browning ( 1993). Characterization of wheat germ protein synthesis initiation factor eIF-4C and comparison of eIF-4C from wheat germ and rabbit reticulocytes. J. Biol. Chem. 268, 24863–24867. Google Scholar

337.

B.S. Tiruneh , B.H. Kim , D.R. Gallie , B. Roy , and A.G. von Arnim ( 2013). The global translation profile in a ribosomal protein mutant resembles that of an eIF3 mutant. BMC Biol. 11, 123. Google Scholar

338.

I. Topisirovic , Y.V. Svitkin , N. Sonenberg , and A.J. Shatkin ( 2011). Cap and cap-binding proteins in the control of gene expression. Wiley Interdiscip. Rev. RNA 2, 277–298. Google Scholar

339.

F. Turck , F. Zilbermann , S.C. Kozma , G. Thomas , and F. Nagy ( 2004). Phytohormones participate in an S6 kinase signal transduction pathway in Arabidopsis. Plant Physiol. 134, 1527–1535. Google Scholar

340.

M.V. Turkina , H. Klang Årstrand , and A.V. Vener ( 2011). Differential phosphorylation of ribosomal proteins in Arabidopsis thaliana plants during day and night. PLoS One 6, e29307. Google Scholar

341.

S. Ude , J. Lassak , A.L. Starosta , T. Kraxenberger , D.N. Wilson , and K. Jung ( 2013). Translation elongation factor EF-P alleviates ribosome stalling at polyproline stretches. Science 339, 82–85. Google Scholar

342.

P. Vain , V. Thole , B. Worland , M. Opanowicz , M.S. Bush , and J.H. Doonan ( 2011). A T-DNA mutation in the RNA helicase eIF4A confers a dose-dependent dwarfing phenotype in Brachypodium distachyon. Plant J. 66, 929–940. Google Scholar

343.

L.S. Valasek ( 2012). ‘Ribozoomin’-translation initiation from the perspective of the ribosome-bound eukaryotic initiation factors (eIFs). Curr. Protein Pept. Sci. 13, 305–330. Google Scholar

344.

D.M. Valenzuela , A. Chaudhuri , and U. Maitra ( 1982). Eukaryotic ribosomal subunit anti-association activity of calf liver is contained in a single polypeptide chain protein of Mr = 25,500 (eukaryotic initiation factor 6). J. Biol. Chem. 257, 7712–7719. Google Scholar

345.

I.A. Valouev , V.V. Kushnirov , and M.D. Ter-Avanesyan ( 2002). Yeast polypeptide chain release factors eRF1 and eRF3 are involved in cytoskeleton organization and cell cycle regulation. Cell Motil. Cytoskeleton 52, 161–173. Google Scholar

346.

A. van Heerden , and K.S. Browning ( 1994). Expression in Escherichia coli of the two subunits of the isozyme form of wheat germ protein synthesis initiation factor 4F. Purification of the subunits and formation of an enzymatically active complex. J. Biol. Chem. 269, 17454–17457. Google Scholar

347.

D.P.S. Verma , and J. Chatterjee (2009). TORing with cell cycle, nutrients, stress and growth. In Signal Crosstalk in Plant Stress Responses, K. Yoshioka and K. Shinozaki , eds (New York, NY: Wiley), pp. 161–180. Google Scholar

348.

A. Verschoor , S. Srivastava , R. Grassucci , and J. Frank ( 1996). Native 3D structure of eukaryotic 80s ribosome: morphological homology with E. coli 70S ribosome. J. Cell Biol. 133, 495–505. Google Scholar

349.

F. Voigts-Hoffmann , S. Klinge , and N. Ban ( 2012). Structural insights into eukaryotic ribosomes and the initiation of translation. Curr. Opin. Struct. Biol. 22, 768–777. Google Scholar

350.

A.G. von Arnim , and D.A. Chamovitz ( 2003). Protein homeostasis: a degrading role for Int6/eIF3e. Curr. Biol. 13, R323–325. Google Scholar

351.

A.G. von Arnim , Q. Jia , and J.N. Vaughn ( 2014). Regulation of plant translation by upstream open reading frames. Plant Sci. 214, 1–12. Google Scholar

352.

S.E. Walker , F. Zhou , S.F. Mitchell , V.S. Larson , L. Valasek , A.G. Hinnebusch , and J.R. Lorsch ( 2012). Yeast eIF4B binds to the head of the 40S ribosomal subunit and promotes mRNA recruitment through its N-terminal and internal repeat domains. RNA 9, 191–207. Google Scholar

353.

Y. Wamboldt , S. Mohammed , C. Elowsky , C. Wittgren , W.B. de Paula , and S.A. Mackenzie ( 2009). Participation of leaky ribosome scanning in protein dual targeting by alternative translation initiation in higher plants. Plant Cell 21, 157–167. Google Scholar

354.

A. Wang , and S. Krishnaswamy ( 2012). Eukaryotic translation initiation factor 4E-mediated recessive resistance to plant viruses and its utility in crop improvement. Mol. Plant Pathol. 13, 795–803. Google Scholar

355.

G. Wang , J. Zhang , X. Fan , X. Sun , H. Qin , N. Xu , M. Zhong , Z. Qiao , Y. Tang , and R. Song ( 2014). Proline responding1 plays a critical role in regulating general protein synthesis and the cell cycle in maize. Plant Cell 26, 2582–2600. Google Scholar

356.

J. Wang , P. Lan , H. Gao , L. Zheng , W. Li , and W. Schmidt ( 2013). Expression changes of ribosomal proteins in phosphate- and iron-deficient Arabidopsis roots predict stress-specific alterations in ribosome composition. BMC Genomics 14, 783. Google Scholar

357.

L. Wang , C. Xu , C. Wang , and Y. Wang ( 2012). Characterization of a eukaryotic translation initiation factor 5A homolog from Tamarix androssowii involved in plant abiotic stress tolerance. BMC Plant Biol. 12, 118. Google Scholar

358.

T.W. Wang , L. Lu , C.G. Zhang , C. Taylor , and J.E. Thompson ( 2003). Pleiotropic effects of suppressing deoxyhypusine synthase expression in Arabidopsis thaiiana. Plant Mol. Biol. 52, 1223–1235. Google Scholar

359.

X. Wang , and R. Grumet ( 2004). Identification and characterization of proteins that interact with the carboxy terminus of poly(A)-binding protein and inhibit translation in vitro. Plant Mol. Biol. 54, 85–98. Google Scholar

360.

J.R. Warner , and K.B. McIntosh ( 2009). How common are extraribosomal functions of ribosomal proteins? Mol. Cell 34, 3–11. Google Scholar

361.

C. Webster , R.L. Gaut , K.S. Browning , J.M. Ravel , and J.K.M. Roberts ( 1991). Hypoxia enhances phosphorylation of eukaryotic initiation factor 4A in maize root tips. J. Biol. Chem. 266, 23341–23346. Google Scholar

362.

C.C. Wei , M.L. Balasta , J.H. Ren , and D.J. Goss ( 1998). Wheat germ poly(A) binding protein enhances the binding affinity of eukaryotic initiation factor 4F and (iso)4F for cap analogues. Biochemistry 37, 1910–1916. Google Scholar

363.

Z. Wei , Y. Xue , H. Xu , and W. Gong ( 2006). Crystal structure of the C-terminal domain of S. cerevisiae eIF5. J. Mol. Biol. 359, 1–9. Google Scholar

364.

A.J. Williams , J. Werner-Fraczek , I.F. Chang , and J. Bailey-Serres ( 2003). Regulated phosphorylation of 40S ribosomal protein S6 in root tips of maize. Plant Physiol. 132, 2086–2097. Google Scholar

365.

D.N. Wilson , and J.H. Doudna Cate ( 2012). The structure and function of the eukaryotic ribosome. Cold Spring Harb. Perspect. Biol. 4, a011536. Google Scholar

366.

X. Wu , M. Liu , B. Downie , C. Liang , G. Ji , Q.Q. Li , and A.G. Hunt ( 2011). Genome-wide landscape of polyadenylation in Arabidopsis provides evidence for extensive alternative polyadenylation. Proc. Natl. Acad. Sci. USA 108, 12533–12538. Google Scholar

367.

C. Xia , Y.J. Wang , W.Q. Li , Y.R. Chen , Y. Deng , X.Q. Zhang , L.Q. Chen , and D. Ye ( 2010). The Arabidopsis eukaryotic translation initiation factor 3, subunit f (AteIF3f), is required for pollen germination and embryogenesis. Plant J. 63, 189–202. Google Scholar

368.

Y. Xiong , and J. Sheen ( 2012). Rapamycin and glucose-target of rapamycin (TOR) protein signaling in plants. J. Biol. Chem. 287, 2836–2842. Google Scholar

369.

Y. Xiong , and J. Sheen ( 2013). Moving beyond translation: glucose-TOR signaling in the transcriptional control of cell cycle. Cell Cycle 12, 1989–1990. Google Scholar

370.

Y. Xiong , and J. Sheen ( 2014). The role of target of rapamycin signaling networks in plant growth and metabolism. Plant Physiol. 164, 499–512. Google Scholar

371.

Y. Xiong , M. McCormack , L. Li , Q. Hall , C. Xiang , and J. Sheen ( 2013). Glucose-TOR signalling reprograms the transcripto me and activates meristems. Nature 496, 181–186. Google Scholar

372.

S. Xue , and M. Barna ( 2012). Specialized ribosomes: a new frontier in gene regulation and organismal biology. Nat. Rev. Mol Cell Biol. 13, 355–369. Google Scholar

373.

A. Yahalom , T.H. Kim , E. Winter , B. Karniol , A.G. Von Arnim , and D.A. Chamovitz ( 2001). Arabidopsis eIF3e (INT-6) associates with both eIF3c and the COP9 signalosome subunit CSN7. J. Biol. Chem. 276, 334–340. Google Scholar

374.

A. Yahalom , T.H. Kim , B. Roy , R. Singer , A.G. Von Arnim , and D.A. Chamovitz ( 2008). Arabidopsis eIF3e is regulated by the COP9 signalosome and has an impact on development and protein transíation. Plant J. 53, 300–311. Google Scholar

375.

Y.Y. Yamamoto , T. Yoshitsugu , T. Sakurai , M. Seki , K. Shinozaki , and J. Obokata ( 2009). Heterogeneity of Arabidopsis core promoters revealed by high-density TSS analysis. Plant J. 60, 350–362. Google Scholar

376.

H. Yumak , M.A. Khan , and D.J. Goss ( 2010). Poly(A) tail affects equilibrium and thermodynamic behavior of tobacco etch virus mRNA with translation initiation factors eIF4F, eIF4B and PABP. Biochim. Biophys. Acta. 1799, 653–658. Google Scholar

377.

G. Yusupova , and M. Yusupov ( 2014). High-resolution structure of the eukaryotic 80S ribosome. Annu. Rev. Biochem 83, 467–486. Google Scholar

378.

M.E. Zanetti , I.F. Chang , F. Gong , D.W. Galbraith , and J. Bailey-Serres ( 2005). Immunopurification of polyribosomal complexes of Arabidopsis for global analysis of gene expression. Plant Physiol. 138, 624–635. Google Scholar

379.

J. Zhang , Z. Mao , and K. Chong ( 2013). A global profiling of uncapped mRNAs under cold stress reveals specific decay patterns and endonucleolytic cleavages in Brachypodium distachyon. Genome Biol 14, R92. Google Scholar

380.

Y. Zhang , S. Liu , G. Lajoie , and A.R. Merrill ( 2008a). The role of the diphthamide-containing loop within eukaryotic elongation factor 2 in ADP-ribosylation by Pseudomonas aeruginosa exotoxin A. Biochem. J. 413, 163–174. Google Scholar

381.

Y. Zhang , Y. Wang , K. Kanyuka , M.A. Parry , S.J. Powers , and N.G. Halford ( 2008b). GCN2-dependent phosphorylation of eukaryotic translation initiation factor-2α in Arabidopsis. J. Exp. Bot. 59, 3131–3141. Google Scholar

382.

Y.H. Zhang , J.R. Dickinson , M.J. Paul , and N.G. Halford ( 2003). Molecular cloning of an Arabidopsis homologue of GCN2, a protein kinase involved in co-ordinated response to amino acid starvation. Planta 217, 668–675. Google Scholar

383.

C. Zhou , F. Arslan , S. Wee , S. Krishnan , A.R. Ivanov , A. Oliva , J. Leatherwood , and D.A. Wolf ( 2005). PCI proteins eIF3e and eIF3m define distinct translation initiation factor 3 complexes. BMC Biol. 3, 14. Google Scholar

384.

F. Zhou , B. Roy , and A.G. Von Arnim ( 2010a). Translation reinitiation and development are compromised in similar ways by mutations in translation initiation factor eIF3h and the ribosomal protein RPL24. BMC Plant Biol. 10, 193. Google Scholar

385.

F. Zhou , B. Roy , J.R. Dunlap , R. Enganti , and A.G. von Arnim ( 2014a). Translational control of Arabidopsis meristem stability and organogenesis by the eukaryotic translation factor eIF3h. PLoS One 9, e95396. Google Scholar

386.

F. Zhou , S.E. Walker , S.F. Mitchell , J.R. Lorsch , and A.G. Hinnebusch ( 2014b). Identification and characterization of functionally critical, conserved motifs in the internal repeats and N-terminal domain of yeast translation initiation factor 4B (yeIF4B). J. Biol. Chem. 289, 1704–1722. Google Scholar

387.

X. Zhou , P. Cooke , and L. Li ( 2010b). Eukaryotic release factor 1–2 affects Arabidopsis responses to glucose and phytohormones during germination and early seedling development. J. Exp. Bot. 61, 357–367. Google Scholar

388.

X. Zhou , T.H. Sun , N. Wang , H.Q. Ling , S. Lu , and L. Li ( 2010c). The cauliflower Orange gene enhances petiole elongation by suppressing expression of eukaryotic release factor 1. New Phytol. 190, 89–100. Google Scholar

389.

R. Zoncu , A. Efeyan , and D.M. Sabatini ( 2011). mTOR: from growth signal integration to cancer, diabetes and ageing. Nat. Rev. Mol. Cell Biol. 12, 21–35. Google Scholar
© 2015 American Society of Plant Biologists
Karen S. Browning and Julia Bailey-Serres "Mechanism of Cytoplasmic mRNA Translation," The Arabidopsis Book 2015(13), (24 April 2015). https://doi.org/10.1199/tab.0176
Published: 24 April 2015
JOURNAL ARTICLE
PAGES


Share
SHARE
RIGHTS & PERMISSIONS
Get copyright permission
Back to Top