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The RNA-binding protein ELAVL1/HuR is essential for mouse spermatogenesis, acting both at meiotic and postmeiotic stages

Posttranscriptional mechanisms are crucial to regulate spermatogenesis. Accurate protein synthesis during germ cell development relies on RNA binding proteins that control the storage, stability, and translation of mRNAs in a tightly and temporally regulated manner. Here, we focused on the RNA bindi...

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Autores principales: Chi, Mai Nguyen, Auriol, Jacques, Jégou, Bernard, Kontoyiannis, Dimitris L., Turner, James M.A., de Rooij, Dirk G., Morello, Dominique
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3154883/
https://www.ncbi.nlm.nih.gov/pubmed/21737689
http://dx.doi.org/10.1091/mbc.E11-03-0212
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author Chi, Mai Nguyen
Auriol, Jacques
Jégou, Bernard
Kontoyiannis, Dimitris L.
Turner, James M.A.
de Rooij, Dirk G.
Morello, Dominique
author_facet Chi, Mai Nguyen
Auriol, Jacques
Jégou, Bernard
Kontoyiannis, Dimitris L.
Turner, James M.A.
de Rooij, Dirk G.
Morello, Dominique
author_sort Chi, Mai Nguyen
collection PubMed
description Posttranscriptional mechanisms are crucial to regulate spermatogenesis. Accurate protein synthesis during germ cell development relies on RNA binding proteins that control the storage, stability, and translation of mRNAs in a tightly and temporally regulated manner. Here, we focused on the RNA binding protein Embryonic Lethal Abnormal Vision (ELAV) L1/Human antigen R (HuR) known to be a key regulator of posttranscriptional regulation in somatic cells but the function of which during gametogenesis has never been investigated. In this study, we have used conditional loss- and gain-of-function approaches to address this issue in mice. We show that targeted deletion of HuR specifically in germ cells leads to male but not female sterility. Mutant males are azoospermic because of the extensive death of spermatocytes at meiotic divisions and failure of spermatid elongation. The latter defect is also observed upon HuR overexpression. To elucidate further the molecular mechanisms underlying spermatogenesis defects in HuR-deleted and -overexpressing testes, we undertook a target gene approach and discovered that heat shock protein (HSP)A2/HSP70-2, a crucial regulator of spermatogenesis, was down-regulated in both situations. HuR specifically binds hspa2 mRNA and controls its expression at the translational level in germ cells. Our study provides the first genetic evidence of HuR involvement during spermatogenesis and reveals Hspa2 as a target for HuR.
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spelling pubmed-31548832011-10-30 The RNA-binding protein ELAVL1/HuR is essential for mouse spermatogenesis, acting both at meiotic and postmeiotic stages Chi, Mai Nguyen Auriol, Jacques Jégou, Bernard Kontoyiannis, Dimitris L. Turner, James M.A. de Rooij, Dirk G. Morello, Dominique Mol Biol Cell Articles Posttranscriptional mechanisms are crucial to regulate spermatogenesis. Accurate protein synthesis during germ cell development relies on RNA binding proteins that control the storage, stability, and translation of mRNAs in a tightly and temporally regulated manner. Here, we focused on the RNA binding protein Embryonic Lethal Abnormal Vision (ELAV) L1/Human antigen R (HuR) known to be a key regulator of posttranscriptional regulation in somatic cells but the function of which during gametogenesis has never been investigated. In this study, we have used conditional loss- and gain-of-function approaches to address this issue in mice. We show that targeted deletion of HuR specifically in germ cells leads to male but not female sterility. Mutant males are azoospermic because of the extensive death of spermatocytes at meiotic divisions and failure of spermatid elongation. The latter defect is also observed upon HuR overexpression. To elucidate further the molecular mechanisms underlying spermatogenesis defects in HuR-deleted and -overexpressing testes, we undertook a target gene approach and discovered that heat shock protein (HSP)A2/HSP70-2, a crucial regulator of spermatogenesis, was down-regulated in both situations. HuR specifically binds hspa2 mRNA and controls its expression at the translational level in germ cells. Our study provides the first genetic evidence of HuR involvement during spermatogenesis and reveals Hspa2 as a target for HuR. The American Society for Cell Biology 2011-08-15 /pmc/articles/PMC3154883/ /pubmed/21737689 http://dx.doi.org/10.1091/mbc.E11-03-0212 Text en © 2011 Chi et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Chi, Mai Nguyen
Auriol, Jacques
Jégou, Bernard
Kontoyiannis, Dimitris L.
Turner, James M.A.
de Rooij, Dirk G.
Morello, Dominique
The RNA-binding protein ELAVL1/HuR is essential for mouse spermatogenesis, acting both at meiotic and postmeiotic stages
title The RNA-binding protein ELAVL1/HuR is essential for mouse spermatogenesis, acting both at meiotic and postmeiotic stages
title_full The RNA-binding protein ELAVL1/HuR is essential for mouse spermatogenesis, acting both at meiotic and postmeiotic stages
title_fullStr The RNA-binding protein ELAVL1/HuR is essential for mouse spermatogenesis, acting both at meiotic and postmeiotic stages
title_full_unstemmed The RNA-binding protein ELAVL1/HuR is essential for mouse spermatogenesis, acting both at meiotic and postmeiotic stages
title_short The RNA-binding protein ELAVL1/HuR is essential for mouse spermatogenesis, acting both at meiotic and postmeiotic stages
title_sort rna-binding protein elavl1/hur is essential for mouse spermatogenesis, acting both at meiotic and postmeiotic stages
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3154883/
https://www.ncbi.nlm.nih.gov/pubmed/21737689
http://dx.doi.org/10.1091/mbc.E11-03-0212
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