The germ cell-specific RNA binding protein RBM46 is essential for spermatogonial differentiation in mice.

Control over gene expression is exerted, in multiple stages of spermatogenesis, at the post-transcriptional level by RNA binding proteins (RBPs). We identify here an essential role in mammalian spermatogenesis and male fertility for 'RNA binding protein 46' (RBM46). A highly evolutionarily...

Full description

Bibliographic Details
Main Authors: Natoya J Peart, Taylor A Johnson, Sungkyoung Lee, Matthew J Sears, Fang Yang, Mathieu Quesnel-Vallières, Huijuan Feng, Yocelyn Recinos, Yoseph Barash, Chaolin Zhang, Brian P Hermann, P Jeremy Wang, Christopher B Geyer, Russ P Carstens
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2022-09-01
Series:PLoS Genetics
Online Access:https://doi.org/10.1371/journal.pgen.1010416
_version_ 1797823697208213504
author Natoya J Peart
Taylor A Johnson
Sungkyoung Lee
Matthew J Sears
Fang Yang
Mathieu Quesnel-Vallières
Huijuan Feng
Yocelyn Recinos
Yoseph Barash
Chaolin Zhang
Brian P Hermann
P Jeremy Wang
Christopher B Geyer
Russ P Carstens
author_facet Natoya J Peart
Taylor A Johnson
Sungkyoung Lee
Matthew J Sears
Fang Yang
Mathieu Quesnel-Vallières
Huijuan Feng
Yocelyn Recinos
Yoseph Barash
Chaolin Zhang
Brian P Hermann
P Jeremy Wang
Christopher B Geyer
Russ P Carstens
author_sort Natoya J Peart
collection DOAJ
description Control over gene expression is exerted, in multiple stages of spermatogenesis, at the post-transcriptional level by RNA binding proteins (RBPs). We identify here an essential role in mammalian spermatogenesis and male fertility for 'RNA binding protein 46' (RBM46). A highly evolutionarily conserved gene, Rbm46 is also essential for fertility in both flies and fish. We found Rbm46 expression was restricted to the mouse germline, detectable in males in the cytoplasm of premeiotic spermatogonia and meiotic spermatocytes. To define its requirement for spermatogenesis, we generated Rbm46 knockout (KO, Rbm46-/-) mice; although male Rbm46-/- mice were viable and appeared grossly normal, they were infertile. Testes from adult Rbm46-/- mice were small, with seminiferous tubules containing only Sertoli cells and few undifferentiated spermatogonia. Using genome-wide unbiased high throughput assays RNA-seq and 'enhanced crosslinking immunoprecipitation' coupled with RNA-seq (eCLIP-seq), we discovered RBM46 could bind, via a U-rich conserved consensus sequence, to a cohort of mRNAs encoding proteins required for completion of differentiation and subsequent meiotic initiation. In summary, our studies support an essential role for RBM46 in regulating target mRNAs during spermatogonia differentiation prior to the commitment to meiosis in mice.
first_indexed 2024-03-13T10:26:45Z
format Article
id doaj.art-53361225d7ba4d6abbf2e4eaf7ec0fd2
institution Directory Open Access Journal
issn 1553-7390
1553-7404
language English
last_indexed 2024-03-13T10:26:45Z
publishDate 2022-09-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS Genetics
spelling doaj.art-53361225d7ba4d6abbf2e4eaf7ec0fd22023-05-19T05:31:05ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042022-09-01189e101041610.1371/journal.pgen.1010416The germ cell-specific RNA binding protein RBM46 is essential for spermatogonial differentiation in mice.Natoya J PeartTaylor A JohnsonSungkyoung LeeMatthew J SearsFang YangMathieu Quesnel-VallièresHuijuan FengYocelyn RecinosYoseph BarashChaolin ZhangBrian P HermannP Jeremy WangChristopher B GeyerRuss P CarstensControl over gene expression is exerted, in multiple stages of spermatogenesis, at the post-transcriptional level by RNA binding proteins (RBPs). We identify here an essential role in mammalian spermatogenesis and male fertility for 'RNA binding protein 46' (RBM46). A highly evolutionarily conserved gene, Rbm46 is also essential for fertility in both flies and fish. We found Rbm46 expression was restricted to the mouse germline, detectable in males in the cytoplasm of premeiotic spermatogonia and meiotic spermatocytes. To define its requirement for spermatogenesis, we generated Rbm46 knockout (KO, Rbm46-/-) mice; although male Rbm46-/- mice were viable and appeared grossly normal, they were infertile. Testes from adult Rbm46-/- mice were small, with seminiferous tubules containing only Sertoli cells and few undifferentiated spermatogonia. Using genome-wide unbiased high throughput assays RNA-seq and 'enhanced crosslinking immunoprecipitation' coupled with RNA-seq (eCLIP-seq), we discovered RBM46 could bind, via a U-rich conserved consensus sequence, to a cohort of mRNAs encoding proteins required for completion of differentiation and subsequent meiotic initiation. In summary, our studies support an essential role for RBM46 in regulating target mRNAs during spermatogonia differentiation prior to the commitment to meiosis in mice.https://doi.org/10.1371/journal.pgen.1010416
spellingShingle Natoya J Peart
Taylor A Johnson
Sungkyoung Lee
Matthew J Sears
Fang Yang
Mathieu Quesnel-Vallières
Huijuan Feng
Yocelyn Recinos
Yoseph Barash
Chaolin Zhang
Brian P Hermann
P Jeremy Wang
Christopher B Geyer
Russ P Carstens
The germ cell-specific RNA binding protein RBM46 is essential for spermatogonial differentiation in mice.
PLoS Genetics
title The germ cell-specific RNA binding protein RBM46 is essential for spermatogonial differentiation in mice.
title_full The germ cell-specific RNA binding protein RBM46 is essential for spermatogonial differentiation in mice.
title_fullStr The germ cell-specific RNA binding protein RBM46 is essential for spermatogonial differentiation in mice.
title_full_unstemmed The germ cell-specific RNA binding protein RBM46 is essential for spermatogonial differentiation in mice.
title_short The germ cell-specific RNA binding protein RBM46 is essential for spermatogonial differentiation in mice.
title_sort germ cell specific rna binding protein rbm46 is essential for spermatogonial differentiation in mice
url https://doi.org/10.1371/journal.pgen.1010416
work_keys_str_mv AT natoyajpeart thegermcellspecificrnabindingproteinrbm46isessentialforspermatogonialdifferentiationinmice
AT taylorajohnson thegermcellspecificrnabindingproteinrbm46isessentialforspermatogonialdifferentiationinmice
AT sungkyounglee thegermcellspecificrnabindingproteinrbm46isessentialforspermatogonialdifferentiationinmice
AT matthewjsears thegermcellspecificrnabindingproteinrbm46isessentialforspermatogonialdifferentiationinmice
AT fangyang thegermcellspecificrnabindingproteinrbm46isessentialforspermatogonialdifferentiationinmice
AT mathieuquesnelvallieres thegermcellspecificrnabindingproteinrbm46isessentialforspermatogonialdifferentiationinmice
AT huijuanfeng thegermcellspecificrnabindingproteinrbm46isessentialforspermatogonialdifferentiationinmice
AT yocelynrecinos thegermcellspecificrnabindingproteinrbm46isessentialforspermatogonialdifferentiationinmice
AT yosephbarash thegermcellspecificrnabindingproteinrbm46isessentialforspermatogonialdifferentiationinmice
AT chaolinzhang thegermcellspecificrnabindingproteinrbm46isessentialforspermatogonialdifferentiationinmice
AT brianphermann thegermcellspecificrnabindingproteinrbm46isessentialforspermatogonialdifferentiationinmice
AT pjeremywang thegermcellspecificrnabindingproteinrbm46isessentialforspermatogonialdifferentiationinmice
AT christopherbgeyer thegermcellspecificrnabindingproteinrbm46isessentialforspermatogonialdifferentiationinmice
AT russpcarstens thegermcellspecificrnabindingproteinrbm46isessentialforspermatogonialdifferentiationinmice
AT natoyajpeart germcellspecificrnabindingproteinrbm46isessentialforspermatogonialdifferentiationinmice
AT taylorajohnson germcellspecificrnabindingproteinrbm46isessentialforspermatogonialdifferentiationinmice
AT sungkyounglee germcellspecificrnabindingproteinrbm46isessentialforspermatogonialdifferentiationinmice
AT matthewjsears germcellspecificrnabindingproteinrbm46isessentialforspermatogonialdifferentiationinmice
AT fangyang germcellspecificrnabindingproteinrbm46isessentialforspermatogonialdifferentiationinmice
AT mathieuquesnelvallieres germcellspecificrnabindingproteinrbm46isessentialforspermatogonialdifferentiationinmice
AT huijuanfeng germcellspecificrnabindingproteinrbm46isessentialforspermatogonialdifferentiationinmice
AT yocelynrecinos germcellspecificrnabindingproteinrbm46isessentialforspermatogonialdifferentiationinmice
AT yosephbarash germcellspecificrnabindingproteinrbm46isessentialforspermatogonialdifferentiationinmice
AT chaolinzhang germcellspecificrnabindingproteinrbm46isessentialforspermatogonialdifferentiationinmice
AT brianphermann germcellspecificrnabindingproteinrbm46isessentialforspermatogonialdifferentiationinmice
AT pjeremywang germcellspecificrnabindingproteinrbm46isessentialforspermatogonialdifferentiationinmice
AT christopherbgeyer germcellspecificrnabindingproteinrbm46isessentialforspermatogonialdifferentiationinmice
AT russpcarstens germcellspecificrnabindingproteinrbm46isessentialforspermatogonialdifferentiationinmice