Role of miR-34c microRNA in the late steps of spermatogenesis.
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.
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.
Frantz
F
Bouhallier
Nathalie
N
Allioli
Fabrice
F
Lavial
Frédéric
F
Chalmel
Marie-Hélène
MH
Perrard
Philippe
P
Durand
Jacques
J
Samarut
Bertrand
B
Pain
Jean-Pierre
JP
Rouault
D000818:Animals; D045744:Cell Line, Tumor; D053595:Embryonic Stem Cells / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D022661:RNA, Untranslated / Q000378:metabolism; D051883:Receptor, Notch2 / Q000378:metabolism; D013091:Spermatogenesis / Q000235:genetics*; D014162:Transfection
D035683:MicroRNAs; D022661:RNA, Untranslated; D051883:Receptor, Notch2