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9 April 2022 Noncanonical functions of PIWIL1/piRNAs in animal male germ cells and human diseases
Xin Wang, Lan-Tao Gou, Mo-Fang Liu
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Abstract

PIWI proteins and PIWI-interacting RNAs (piRNAs) are specifically expressed in animal germlines and play essential roles during gametogenesis in animals. The primary function of PIWI/piRNAs is known to silence transposable elements for protecting genome integrity in animal germlines, while their roles beyond silencing transposons are also documented by us and others. In particular, we show that mouse PIWIL1 (MIWI)/piRNAs play a dual role in regulating protein-coding genes in mouse spermatids through interacting with different protein factors in a developmental stage-dependent manner, including translationally activating a subset of AU-rich element-containing mRNAs in round spermatids and inducing massive mRNA degradation in late spermatids. We further show that MIWI is eliminated through the ubiquitin-26S proteasome pathway during late spermiogenesis. By exploring the biological function of MIWI ubiquitination by APC/C, we identified ubiquitination-deficient mutations in human PIWIL1 of infertile men and further established their causative role in male infertility in mouse model, supporting PIWIL1 as a human male infertility-relevant gene. Additionally, we reported that PIWIL1, aberrantly induced in human tumors, functions as an oncoprotein in a piRNA-independent manner in cancer cells. In the current review, we summarize our latest findings regarding the roles and mechanisms of PIWIL1 and piRNAs in mouse spermatids and human diseases, and discuss the related works in the field.

Summary Sentence

Beyond the primary function of silencing transposons, PIWI/piRNAs also play diverse roles in animal germ cells and human diseases.

© The Author(s) 2022. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Xin Wang, Lan-Tao Gou, and Mo-Fang Liu "Noncanonical functions of PIWIL1/piRNAs in animal male germ cells and human diseases," Biology of Reproduction 107(1), 101-108, (9 April 2022). https://doi.org/10.1093/biolre/ioac073
Received: 23 December 2021; Accepted: 31 March 2022; Published: 9 April 2022
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KEYWORDS
cancer cells
Male infertility
MIWI
PIWIL1/piRNAs
spermiogenesis
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