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yama, a mutant allele of Mov10l1, disrupts retrotransposon silencing and piRNA biogenesis

Piwi-interacting RNAs (piRNAs) play critical roles in protecting germline genome integrity and promoting normal spermiogenic differentiation. In mammals, there are two populations of piRNAs: pre-pachytene and pachytene. Transposon-rich pre-pachytene piRNAs are expressed in fetal and perinatal germ c...

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Autores principales: Guan, Yongjuan, Keeney, Scott, Jain, Devanshi, Wang, P. Jeremy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946307/
https://www.ncbi.nlm.nih.gov/pubmed/33635934
http://dx.doi.org/10.1371/journal.pgen.1009265
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author Guan, Yongjuan
Keeney, Scott
Jain, Devanshi
Wang, P. Jeremy
author_facet Guan, Yongjuan
Keeney, Scott
Jain, Devanshi
Wang, P. Jeremy
author_sort Guan, Yongjuan
collection PubMed
description Piwi-interacting RNAs (piRNAs) play critical roles in protecting germline genome integrity and promoting normal spermiogenic differentiation. In mammals, there are two populations of piRNAs: pre-pachytene and pachytene. Transposon-rich pre-pachytene piRNAs are expressed in fetal and perinatal germ cells and are required for retrotransposon silencing, whereas transposon-poor pachytene piRNAs are expressed in spermatocytes and round spermatids and regulate mRNA transcript levels. MOV10L1, a germ cell-specific RNA helicase, is essential for the production of both populations of piRNAs. Although the requirement of the RNA helicase domain located in the MOV10L1 C-terminal region for piRNA biogenesis is well known, its large N-terminal region remains mysterious. Here we report a novel Mov10l1 mutation, named yama, in the Mov10l1 N-terminal region. The yama mutation results in a single amino acid substitution V229E. The yama mutation causes meiotic arrest, de-repression of transposable elements, and male sterility because of defects in pre-pachytene piRNA biogenesis. Moreover, restricting the Mov10l1 mutation effects to later stages in germ cell development by combining with a postnatal conditional deletion of a complementing wild-type allele causes absence of pachytene piRNAs, accumulation of piRNA precursors, polar conglomeration of piRNA pathway proteins in spermatocytes, and spermiogenic arrest. Mechanistically, the V229E substitution in MOV10L1 reduces its interaction with PLD6, an endonuclease that generates the 5′ ends of piRNA intermediates. Our results uncover an important role for the MOV10L1-PLD6 interaction in piRNA biogenesis throughout male germ cell development.
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spelling pubmed-79463072021-03-19 yama, a mutant allele of Mov10l1, disrupts retrotransposon silencing and piRNA biogenesis Guan, Yongjuan Keeney, Scott Jain, Devanshi Wang, P. Jeremy PLoS Genet Research Article Piwi-interacting RNAs (piRNAs) play critical roles in protecting germline genome integrity and promoting normal spermiogenic differentiation. In mammals, there are two populations of piRNAs: pre-pachytene and pachytene. Transposon-rich pre-pachytene piRNAs are expressed in fetal and perinatal germ cells and are required for retrotransposon silencing, whereas transposon-poor pachytene piRNAs are expressed in spermatocytes and round spermatids and regulate mRNA transcript levels. MOV10L1, a germ cell-specific RNA helicase, is essential for the production of both populations of piRNAs. Although the requirement of the RNA helicase domain located in the MOV10L1 C-terminal region for piRNA biogenesis is well known, its large N-terminal region remains mysterious. Here we report a novel Mov10l1 mutation, named yama, in the Mov10l1 N-terminal region. The yama mutation results in a single amino acid substitution V229E. The yama mutation causes meiotic arrest, de-repression of transposable elements, and male sterility because of defects in pre-pachytene piRNA biogenesis. Moreover, restricting the Mov10l1 mutation effects to later stages in germ cell development by combining with a postnatal conditional deletion of a complementing wild-type allele causes absence of pachytene piRNAs, accumulation of piRNA precursors, polar conglomeration of piRNA pathway proteins in spermatocytes, and spermiogenic arrest. Mechanistically, the V229E substitution in MOV10L1 reduces its interaction with PLD6, an endonuclease that generates the 5′ ends of piRNA intermediates. Our results uncover an important role for the MOV10L1-PLD6 interaction in piRNA biogenesis throughout male germ cell development. Public Library of Science 2021-02-26 /pmc/articles/PMC7946307/ /pubmed/33635934 http://dx.doi.org/10.1371/journal.pgen.1009265 Text en © 2021 Guan et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Guan, Yongjuan
Keeney, Scott
Jain, Devanshi
Wang, P. Jeremy
yama, a mutant allele of Mov10l1, disrupts retrotransposon silencing and piRNA biogenesis
title yama, a mutant allele of Mov10l1, disrupts retrotransposon silencing and piRNA biogenesis
title_full yama, a mutant allele of Mov10l1, disrupts retrotransposon silencing and piRNA biogenesis
title_fullStr yama, a mutant allele of Mov10l1, disrupts retrotransposon silencing and piRNA biogenesis
title_full_unstemmed yama, a mutant allele of Mov10l1, disrupts retrotransposon silencing and piRNA biogenesis
title_short yama, a mutant allele of Mov10l1, disrupts retrotransposon silencing and piRNA biogenesis
title_sort yama, a mutant allele of mov10l1, disrupts retrotransposon silencing and pirna biogenesis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946307/
https://www.ncbi.nlm.nih.gov/pubmed/33635934
http://dx.doi.org/10.1371/journal.pgen.1009265
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