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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 conserved...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9529142/ https://www.ncbi.nlm.nih.gov/pubmed/36129965 http://dx.doi.org/10.1371/journal.pgen.1010416 |
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author | Peart, Natoya J. Johnson, Taylor A. Lee, Sungkyoung Sears, Matthew J. Yang, Fang Quesnel-Vallières, Mathieu Feng, Huijuan Recinos, Yocelyn Barash, Yoseph Zhang, Chaolin Hermann, Brian P. Wang, P. Jeremy Geyer, Christopher B. Carstens, Russ P. |
author_facet | Peart, Natoya J. Johnson, Taylor A. Lee, Sungkyoung Sears, Matthew J. Yang, Fang Quesnel-Vallières, Mathieu Feng, Huijuan Recinos, Yocelyn Barash, Yoseph Zhang, Chaolin Hermann, Brian P. Wang, P. Jeremy Geyer, Christopher B. Carstens, Russ P. |
author_sort | Peart, Natoya J. |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-9529142 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-95291422022-10-04 The germ cell-specific RNA binding protein RBM46 is essential for spermatogonial differentiation in mice Peart, Natoya J. Johnson, Taylor A. Lee, Sungkyoung Sears, Matthew J. Yang, Fang Quesnel-Vallières, Mathieu Feng, Huijuan Recinos, Yocelyn Barash, Yoseph Zhang, Chaolin Hermann, Brian P. Wang, P. Jeremy Geyer, Christopher B. Carstens, Russ P. PLoS Genet Research Article 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. Public Library of Science 2022-09-21 /pmc/articles/PMC9529142/ /pubmed/36129965 http://dx.doi.org/10.1371/journal.pgen.1010416 Text en © 2022 Peart et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://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 Peart, Natoya J. Johnson, Taylor A. Lee, Sungkyoung Sears, Matthew J. Yang, Fang Quesnel-Vallières, Mathieu Feng, Huijuan Recinos, Yocelyn Barash, Yoseph Zhang, Chaolin Hermann, Brian P. Wang, P. Jeremy Geyer, Christopher B. Carstens, Russ P. The germ cell-specific RNA binding protein RBM46 is essential for spermatogonial differentiation in mice |
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 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9529142/ https://www.ncbi.nlm.nih.gov/pubmed/36129965 http://dx.doi.org/10.1371/journal.pgen.1010416 |
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