Role of miR-34c microRNA in the late steps of spermatogenesis
- Frantz Bouhallier1,
- Nathalie Allioli2,3,
- Fabrice Lavial1,9,
- Frédéric Chalmel4,5,
- Marie-Hélène Perrard1,
- Philippe Durand1,
- Jacques Samarut1,2,6,7,
- Bertrand Pain1,8 and
- Jean-Pierre Rouault1
- 1Ecole Normale Supérieure de Lyon, Institut de Génomique Fonctionnelle de Lyon (IGFL), Université Lyon1, CNRS UMR 5242, INRA UMR1288, F-69364 Lyon, Cedex 07, France
- 2Faculté de Médecine, Institut de Génomique Fonctionnelle de Lyon (IGFL), Centre National de la Recherche Scientifique (CNRS) UMR5242, INRA UMR1288, Plateforme CLARA, 69495 Pierre-Bénite, France
- 3Institut des Sciences Pharmaceutiques et Biologiques (ISPB) de Lyon, Université Claude Bernard Lyon, 69622 Villeurbanne Cedex, France
- 4Groupe d’Étude de la Reproduction Chez l'Homme et les Mammifères (GERHM), Institut National de la Santé et de la Recherche Médicale (Inserm U625), Université Rennes 1, IFR140, Rennes, F-35042, France
- 5UMR-S625, Université Rennes1, Rennes, F-35042, France
- 6Faculté de Médecine Lyon Sud, Université Claude Bernard Lyon1, 69622 Villeurbanne Cedex, France
- 7Unité Médicale d'Oncologie Moléculaire et Transfert (UMOMT), Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon (HCL), 69495 Pierre-Bénite, France
- 8Centre National de la Recherche Scientifique (CNRS), UMR 6247, Institut National de la Santé et de la Recherche Médicale (Inserm), Université de Clermont, U931 Clermont-Ferrand, France
Abstract
Spermatogenesis is a cyclic process in which diploid spermatogonia differentiate into haploid spermatozoa. This process is highly regulated, notably at the post-transcriptional level. MicroRNAs (miRNAs), single-stranded noncoding RNA molecules of about 20–25 nucleotides, are implicated in the regulation of many important biological pathways such as proliferation, apoptosis, and differentiation. We wondered whether miRNAs could play a role during spermatogenesis. The miRNA expression repertoire was tested in germ cells, and we present data showing that miR-34c was highly expressed only in these cells. Furthermore, our findings indicate that in male gonads, miR-34c expression is largely p53 independent in contrast to previous results showing a direct link in somatic cells between the miR-34 family and this tumor suppressor protein. In order to identify target genes involved in germinal lineage differentiation, we overexpressed miR-34c in HeLa cells, analyzed the transcriptome of these modified cells, and noticed a shift of the expression profile toward the germinal lineage. Recently, it has been shown that exogenous expression of Ddx4/Vasa in embryonic chicken stem cells (cESC) induces cESC reprogramming toward a germ cell fate. When we simultaneously expressed miR-34c in such cells, we could detect an up-regulation of germ cell-specific genes whereas the expression of other lineage specific markers remained unchanged. These data suggest that miR-34c could play a role by enhancing the germinal phenotype of cells already committed to this lineage.
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Footnotes
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Reprint requests to: Jean-Pierre Rouault, Ecole Normale Supérieure de Lyon, Institut de Génomique Fonctionnelle de Lyon (IGFL), Université Lyon1, CNRS UMR 5242, INRA UMR1288, F-69364 Lyon, Cedex 07, France; e-mail: jean-pierre.rouault{at}ens-lyon.fr; fax: 33(0)472728992.
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Article published online ahead of print. Article and publication date are at http://www.rnajournal.org/cgi/doi/10.1261/rna.1963810.
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- Received October 16, 2009.
- Accepted December 23, 2009.