The conserved RNA helicase YTHDC2 regulates the transition from proliferation to differentiation in the germline

The switch from mitosis to meiosis is the key event marking onset of differentiation in the germline stem cell lineage. In Drosophila, the translational repressor Bgcn is required for spermatogonia to stop mitosis and transition to meiotic prophase and the spermatocyte state. Here we show that the m...

Full description

Bibliographic Details
Main Authors: Alexis S Bailey, Pedro J Batista, Rebecca S Gold, Y Grace Chen, Dirk G de Rooij, Howard Y Chang, Margaret T Fuller
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2017-10-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/26116
_version_ 1811180692153827328
author Alexis S Bailey
Pedro J Batista
Rebecca S Gold
Y Grace Chen
Dirk G de Rooij
Howard Y Chang
Margaret T Fuller
author_facet Alexis S Bailey
Pedro J Batista
Rebecca S Gold
Y Grace Chen
Dirk G de Rooij
Howard Y Chang
Margaret T Fuller
author_sort Alexis S Bailey
collection DOAJ
description The switch from mitosis to meiosis is the key event marking onset of differentiation in the germline stem cell lineage. In Drosophila, the translational repressor Bgcn is required for spermatogonia to stop mitosis and transition to meiotic prophase and the spermatocyte state. Here we show that the mammalian Bgcn homolog YTHDC2 facilitates a clean switch from mitosis to meiosis in mouse germ cells, revealing a conserved role for YTHDC2 in this critical cell fate transition. YTHDC2-deficient male germ cells enter meiosis but have a mixed identity, maintaining expression of Cyclin A2 and failing to properly express many meiotic markers. Instead of continuing through meiotic prophase, the cells attempt an abnormal mitotic-like division and die. YTHDC2 binds multiple transcripts including Ccna2 and other mitotic transcripts, binds specific piRNA precursors, and interacts with RNA granule components, suggesting that proper progression of germ cells through meiosis is licensed by YTHDC2 through post-transcriptional regulation.
first_indexed 2024-04-11T09:07:34Z
format Article
id doaj.art-c1bb0fbf955f4358a4ae2280819dbc35
institution Directory Open Access Journal
issn 2050-084X
language English
last_indexed 2024-04-11T09:07:34Z
publishDate 2017-10-01
publisher eLife Sciences Publications Ltd
record_format Article
series eLife
spelling doaj.art-c1bb0fbf955f4358a4ae2280819dbc352022-12-22T04:32:36ZengeLife Sciences Publications LtdeLife2050-084X2017-10-01610.7554/eLife.26116The conserved RNA helicase YTHDC2 regulates the transition from proliferation to differentiation in the germlineAlexis S Bailey0https://orcid.org/0000-0001-8838-8625Pedro J Batista1https://orcid.org/0000-0003-1055-2354Rebecca S Gold2https://orcid.org/0000-0002-2408-7716Y Grace Chen3https://orcid.org/0000-0003-3574-5734Dirk G de Rooij4https://orcid.org/0000-0003-3932-4419Howard Y Chang5https://orcid.org/0000-0002-9459-4393Margaret T Fuller6https://orcid.org/0000-0002-3804-4987Department of Developmental Biology, Stanford University School of Medicine, Stanford, United StatesCenter for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, United StatesDepartment of Developmental Biology, Stanford University School of Medicine, Stanford, United StatesCenter for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, United StatesCenter for Reproductive Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsCenter for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, United StatesDepartment of Developmental Biology, Stanford University School of Medicine, Stanford, United StatesThe switch from mitosis to meiosis is the key event marking onset of differentiation in the germline stem cell lineage. In Drosophila, the translational repressor Bgcn is required for spermatogonia to stop mitosis and transition to meiotic prophase and the spermatocyte state. Here we show that the mammalian Bgcn homolog YTHDC2 facilitates a clean switch from mitosis to meiosis in mouse germ cells, revealing a conserved role for YTHDC2 in this critical cell fate transition. YTHDC2-deficient male germ cells enter meiosis but have a mixed identity, maintaining expression of Cyclin A2 and failing to properly express many meiotic markers. Instead of continuing through meiotic prophase, the cells attempt an abnormal mitotic-like division and die. YTHDC2 binds multiple transcripts including Ccna2 and other mitotic transcripts, binds specific piRNA precursors, and interacts with RNA granule components, suggesting that proper progression of germ cells through meiosis is licensed by YTHDC2 through post-transcriptional regulation.https://elifesciences.org/articles/26116germline stem cell lineagemitosis to meiosis transitionpost-transcriptional regulationYTHDC2Bgcnspermatogenesis
spellingShingle Alexis S Bailey
Pedro J Batista
Rebecca S Gold
Y Grace Chen
Dirk G de Rooij
Howard Y Chang
Margaret T Fuller
The conserved RNA helicase YTHDC2 regulates the transition from proliferation to differentiation in the germline
eLife
germline stem cell lineage
mitosis to meiosis transition
post-transcriptional regulation
YTHDC2
Bgcn
spermatogenesis
title The conserved RNA helicase YTHDC2 regulates the transition from proliferation to differentiation in the germline
title_full The conserved RNA helicase YTHDC2 regulates the transition from proliferation to differentiation in the germline
title_fullStr The conserved RNA helicase YTHDC2 regulates the transition from proliferation to differentiation in the germline
title_full_unstemmed The conserved RNA helicase YTHDC2 regulates the transition from proliferation to differentiation in the germline
title_short The conserved RNA helicase YTHDC2 regulates the transition from proliferation to differentiation in the germline
title_sort conserved rna helicase ythdc2 regulates the transition from proliferation to differentiation in the germline
topic germline stem cell lineage
mitosis to meiosis transition
post-transcriptional regulation
YTHDC2
Bgcn
spermatogenesis
url https://elifesciences.org/articles/26116
work_keys_str_mv AT alexissbailey theconservedrnahelicaseythdc2regulatesthetransitionfromproliferationtodifferentiationinthegermline
AT pedrojbatista theconservedrnahelicaseythdc2regulatesthetransitionfromproliferationtodifferentiationinthegermline
AT rebeccasgold theconservedrnahelicaseythdc2regulatesthetransitionfromproliferationtodifferentiationinthegermline
AT ygracechen theconservedrnahelicaseythdc2regulatesthetransitionfromproliferationtodifferentiationinthegermline
AT dirkgderooij theconservedrnahelicaseythdc2regulatesthetransitionfromproliferationtodifferentiationinthegermline
AT howardychang theconservedrnahelicaseythdc2regulatesthetransitionfromproliferationtodifferentiationinthegermline
AT margarettfuller theconservedrnahelicaseythdc2regulatesthetransitionfromproliferationtodifferentiationinthegermline
AT alexissbailey conservedrnahelicaseythdc2regulatesthetransitionfromproliferationtodifferentiationinthegermline
AT pedrojbatista conservedrnahelicaseythdc2regulatesthetransitionfromproliferationtodifferentiationinthegermline
AT rebeccasgold conservedrnahelicaseythdc2regulatesthetransitionfromproliferationtodifferentiationinthegermline
AT ygracechen conservedrnahelicaseythdc2regulatesthetransitionfromproliferationtodifferentiationinthegermline
AT dirkgderooij conservedrnahelicaseythdc2regulatesthetransitionfromproliferationtodifferentiationinthegermline
AT howardychang conservedrnahelicaseythdc2regulatesthetransitionfromproliferationtodifferentiationinthegermline
AT margarettfuller conservedrnahelicaseythdc2regulatesthetransitionfromproliferationtodifferentiationinthegermline