Role of miR-34c microRNA in the late steps of spermatogenesis
Role of miR-34c microRNA in the late steps of spermatogenesis
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DOI：
10.1261/rna.1963810
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发表时间：
2010-04-01
期刊：
影响因子：
4.5
通讯作者：
Rouault, Jean-Pierre
中科院分区：
文献类型：
--
作者：
Bouhallier, Frantz;Allioli, Nathalie;Rouault, Jean-Pierre
精子发生是二倍体精原细胞向单倍体精子分化的一个循环过程。这一过程受到高度调控，特别是在转录后水平。microRNA（miRNAs）是一类长度约为20-25个核苷酸的单链非编码RNA分子，参与细胞增殖、凋亡和分化等重要生物学过程的调控。我们想知道miRNAs是否在精子发生过程中发挥作用。在生殖细胞中检测了miRNA表达谱，我们目前的数据显示miR-34 c仅在这些细胞中高度表达。此外，我们的研究结果表明，在男性性腺中，miR-34 c的表达在很大程度上是p53独立的，而以前的结果显示，在体细胞之间的miR-34家族和这种肿瘤抑制蛋白的直接联系。为了确定参与germinal谱系分化的靶基因，我们在HeLa细胞中过表达miR-34 c，分析了这些修饰细胞的转录组，并注意到表达谱向germinal谱系的转变。最近，已经表明，外源性表达的Ddx 4/Vasa在鸡胚胎干细胞（cESC）诱导cESC重编程向生殖细胞的命运。当我们在这些细胞中同时表达miR-34 c时，我们可以检测到生殖细胞特异性基因的上调，而其他谱系特异性标志物的表达保持不变。这些数据表明，miR-34 c可以通过增强已经定型为该谱系的细胞的生殖表型来发挥作用。
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.