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.
Bouhallier
Frantz
F
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.
Allioli
Nathalie
N
Lavial
Fabrice
F
Chalmel
Frédéric
F
Perrard
Marie-Hélène
MH
Durand
Philippe
P
Samarut
Jacques
J
Pain
Bertrand
B
Rouault
Jean-Pierre
JP
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