European Molecular Biology Laboratory, 6 Rue Jules Horowitz, BP 181 CNRS-UJF-EMBL International Unit (UMI 3265) for Virus Host Cell Interactions (UVHCI), 38042 Grenoble, France.
Dev Growth Differ. 2012 Jan;54(1):78-92. doi: 10.1111/j.1440-169X.2011.01320.x. Epub 2012 Jan 6.
Piwi-interacting RNAs (piRNAs) are a class of small non-coding RNAs expressed in the animal gonads. They are implicated in silencing the genome instability threat posed by mobile genetic elements called transposons. Unlike other small RNAs, which use double-stranded precursors, piRNAs seem to arise from long single-stranded precursor transcripts expressed from discrete genomic regions. In mice, the Piwi pathway is essential for male fertility, and its loss-of-function mutations affect several distinct stages of spermatogenesis. While this small RNA pathway primarily operates post-transcriptionally, it also impacts DNA methylation of target retrotransposon loci, representing an intriguing model of RNA-directed epigenetic control in mammals. Remarkably the Piwi pathway components are specifically localized at germinal granule/nuage, an evolutionarily conserved but still enigmatic ribonucleoprotein compartment in the germline. The inaccessibility of the germline for easy experimental manipulation has meant that this class of RNAs has remained enigmatic. However, recent advances in the use of cell culture models and cell-free systems have greatly advanced our understanding. In this review, we briefly summarize our current understanding of the Piwi pathway, focusing on its developmental regulation, piRNA biogenesis and key function in male germline development from fetal spermatogonial stem cell stage to postnatal haploid spermiogenesis in mice.
Piwi 相互作用 RNA（piRNA）是一类在动物性腺中表达的小非编码 RNA。它们参与沉默由称为转座子的移动遗传元件引起的基因组不稳定性威胁。与使用双链前体的其他小 RNA 不同，piRNA 似乎源自从离散基因组区域表达的长单链前体转录本。在小鼠中，Piwi 途径对于雄性生育力至关重要，其功能丧失突变会影响精子发生的几个不同阶段。虽然这条小 RNA 途径主要在转录后起作用，但它也会影响靶逆转录转座子位点的 DNA 甲基化，代表了哺乳动物中 RNA 指导的表观遗传控制的一个有趣模型。值得注意的是，Piwi 途径的组成部分专门定位于生殖质颗粒/核质，这是一个在生殖系中保守但仍然神秘的进化保守的核糖核蛋白隔室。生殖系不易进行实验操作，这意味着这类 RNA 仍然神秘莫测。然而，最近在使用细胞培养模型和无细胞系统方面的进展极大地促进了我们的理解。在这篇综述中，我们简要总结了我们对 Piwi 途径的当前理解，重点介绍了其在发育调控、piRNA 生物发生以及在从胎儿精原干细胞阶段到小鼠出生后单倍体精子发生的雄性生殖细胞发育中的关键功能。
