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22 April 2017 Nonsense in the testis: multiple roles for nonsense-mediated decay revealed in male reproduction
Clinton C. MacDonald, Petar N. Grozdanov
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Abstract

Nonsense-mediated mRNA decay, or NMD, is a quality control mechanism that identifies cytoplasmic mRNAs containing translational termination (stop) codons in specific contexts—either premature termination codons or unusually long 3′ untranslated regions (UTRs)—and targets them for degradation. In recent studies, researchers in different labs have knocked out important genes involved in NMD, the up-frameshift genes Upf2 and Upf3a, and one component of chromatoid bodies, the Tudor domain-containing protein Tdrd6, and examined the consequences for spermatogenesis. Disruption of Upf2 during early stages of spermatogenesis resulted in disappearance of nearly all spermatogenic cells through loss of NMD. However, disruption of Upf2 during postmeiotic stages resulted in decreased long 3′ UTR-mediated NMD but no interruption of exon junction-associated NMD. This difference in NMD targeting is possibly due to increased expression of Upf3a in postmeiotic germ cells that antagonizes the functions of Upf3b and somehow favors long 3′ UTR-mediated NMD. Tying these all together, loss of Tdrd6, a structural component of the germ cell-specific cytoplasmic structures called chromatoid bodies, also resulted in loss of long 3′ UTR-mediated NMD by interfering with UPF1/UPF2 interactions, delocalizing UPF1, and destroying chromatoid body integrity. These results suggest that chromatoid bodies play a specialized role in modulating the NMD machinery in postmeiotic spermatids.

Summary Sentence

Nonsense-mediated decay is how cells eliminate mRNAs having premature stop codons or long 3′ untranslated regions. Recent findings in male germ cells uncover new mechanisms for nonsensemediated decay that shine light on existing models.

© The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
Clinton C. MacDonald and Petar N. Grozdanov "Nonsense in the testis: multiple roles for nonsense-mediated decay revealed in male reproduction," Biology of Reproduction 96(5), 939-947, (22 April 2017). https://doi.org/10.1093/biolre/iox033
Received: 10 January 2017; Accepted: 20 April 2017; Published: 22 April 2017
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