MIWI/piRNA激活小鼠精子细胞mRNA翻译的新功能机制研究

The Study of MIWI/piRNA-Mediated mRNA Translational Activation during Mouse Spermiogenesis

哺乳动物减数分裂后期的精子发生(spermatogenesis),即精子形成(spermiogenesis),是一个剧烈的细胞形态变化过程。伴随精子细胞中细胞核压缩和染色质重构,基因转录活性将逐渐降低直至完全停止,那些为精子细胞后期阶段发育所需的基因都需要提前转录为信使核糖核酸(mRNA),然后以翻译抑制状态储存在精子细胞中,直到特定发育阶段再被激活翻译,以合成蛋白质发挥作用。这个现象被称为“转录–翻译解偶联”,是精子发生中基因表达调控的一个典型特征。然而,目前对于精子细胞中被抑制的mRNA是如何被翻译激活的还知之甚少。我们当前的这项研究发现,MIWI/piRNA通过与翻译起始因子eIF3f、RNA结合蛋白HuR等因子形成功能性翻译激活复合物,特异性地激活小鼠精子细胞中包含AU序列富含元件(AU-rich element,ARE)mRNA的翻译。此项研究揭示了PIWI/piRNA在精子细胞翻译激活中的新功能,并证明此功能为精子细胞发育和功能性精子生成所必需。

Development of post-meiotic male germ cell cells in animals is known as a complex biochemical and morphological process,which is termed as spermiogenesis.Chromatin condensation results in a drastic inhibition of transcriptional activity in late stages of haploid spermatids,and genes that are required for spermiogenesis need to be transcribed in advance and stored as mRNAs in earlier stages of germ cells.However,it remains largely unclear how such repressed mRNAs become activated during spermiogenesis.Here,we unexpectedly discovered that MIWI/piRNA/eIF3f/HuR super-complex is responsible for activating translation of a subset of spermiogenic mRNAs containing cis-acting AU-rich elements.These findings reveal a critical role of the PIWI/piRNA in translation activation,which is functionally required for spermatid development.