title: The RNA-binding protein ELAVL1/HuR is essential for mouse spermatogenesis, acting both at meiotic and postmeiotic stages.
abstract: 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.
authors: CBD, UMR5547, IFR 109, Université Paul Sabatier, 31062 Toulouse Cedex, France.
authors: Mai Nguyen
authors: MN
authors: Chi
authors: Jacques
authors: J
authors: Auriol
authors: Bernard
authors: B
authors: Jégou
authors: Dimitris L
authors: DL
authors: Kontoyiannis
authors: James M A
authors: JM
authors: Turner
authors: Dirk G
authors: DG
authors: de Rooij
authors: Dominique
authors: D
authors: Morello
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism*; D059447:Cell Cycle Checkpoints; D002454:Cell Differentiation; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D015870:Gene Expression; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D007248:Infertility, Male; D008297:Male; D008540:Meiosis; D051379:Mice; D008822:Mice, Transgenic; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D013087:Spermatids / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D013090:Spermatocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D013091:Spermatogenesis; D013737:Testis / Q000166:cytology* / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D018840:HSP70 Heat-Shock Proteins; C490434:Hspa2 protein, mouse; D016601:RNA-Binding Proteins