Deng Wei, Lin Haifan
Department of Cell Biology, Duke University Medical Center, P.O. Box 3709, DUMC, Durham, NC 27710, USA.
Dev Cell. 2002 Jun;2(6):819-30. doi: 10.1016/s1534-5807(02)00165-x.
The piwi family genes are crucial for stem cell self-renewal, RNA silencing, and translational regulation in diverse organisms. However, their function in mammals remains unexplored. Here we report the cloning of a murine piwi gene (miwi) essential for spermatogenesis. miwi encodes a cytoplasmic protein specifically expressed in spermatocytes and spermatids. miwi(null) mice display spermatogenic arrest at the beginning of the round spermatid stage, resembling the phenotype of CREM, a master regulator of spermiogenesis. Furthermore, mRNAs of ACT (activator of CREM in testis) and CREM target genes are downregulated in miwi(null) testes. Whereas MIWI and CREM do not regulate each other's expression, MIWI complexes with mRNAs of ACT and CREM target genes. Hence, MIWI may control spermiogenesis by regulating the stability of these mRNAs.
Piwi家族基因对于多种生物体中的干细胞自我更新、RNA沉默及翻译调控至关重要。然而,它们在哺乳动物中的功能仍未得到探索。在此,我们报告了一个对精子发生必不可少的小鼠Piwi基因(Miwi)的克隆。Miwi编码一种在精母细胞和精子细胞中特异性表达的细胞质蛋白。Miwi基因敲除小鼠在圆形精子细胞阶段开始时出现精子发生停滞,类似于精子形成的主要调节因子CREM的表型。此外,ACT(睾丸中CREM的激活因子)和CREM靶基因的mRNA在Miwi基因敲除小鼠的睾丸中表达下调。虽然MIWI和CREM不相互调节彼此的表达,但MIWI与ACT和CREM靶基因的mRNA形成复合物。因此,MIWI可能通过调节这些mRNA的稳定性来控制精子形成。