Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
Philos Trans R Soc Lond B Biol Sci. 2013 Jan 5;368(1609):20110338. doi: 10.1098/rstb.2011.0338.
Transposable elements and their fossil sequences occupy about half of the genome in mammals. While most of these selfish mobile elements have been inactivated by truncations and mutations during evolution, some copies remain competent to transpose and/or amplify, posing an ongoing genetic threat. To control such mutagenic sequences, host genomes have developed multiple layers of defence mechanisms, including epigenetic regulation and RNA silencing. Germ cells, in particular, employ the piwi-small RNA pathway, which plays a central and adaptive role in safeguarding the germline genome from retrotransposons. Recent studies have revealed that a class of developmentally regulated genes, which have long been implicated in germ cell specification and differentiation, such as vasa and tudor family genes, play key roles in the piwi pathway to suppress retrotransposons, indicating that the piwi-mediated genome protection is at the core of germline development. Furthermore, while the piwi system primarily operates post-transcriptionally at the RNA level, it also affects the epigenetics of cognate genome loci, offering an intriguing link between small RNAs and transcriptional control in mammals. In this review, we summarize our current understanding of the piwi pathway in mice, which is emerging as a fundamental component of spermatogenesis that ensures male fertility and genome integrity.
转座元件及其化石序列在哺乳动物基因组中约占一半。虽然这些自私的移动元件在进化过程中通过截断和突变而大部分失活，但有些拷贝仍然具有转座和/或扩增的能力，构成了持续的遗传威胁。为了控制这种诱变序列，宿主基因组已经发展出了多层次的防御机制，包括表观遗传调控和 RNA 沉默。生殖细胞，特别是利用 piwi-小 RNA 途径，在保护生殖系基因组免受逆转座子的侵害方面发挥着核心和适应性作用。最近的研究表明，一类发育调控基因，长期以来一直被认为与生殖细胞的特化和分化有关，如 vasa 和 tudor 家族基因，在 piwi 途径中发挥关键作用，抑制逆转座子，表明 piwi 介导的基因组保护是生殖系发育的核心。此外，虽然 piwi 系统主要在 RNA 水平上进行转录后调控，但它也影响同源基因组位点的表观遗传学，为哺乳动物中小 RNA 和转录调控之间提供了一个有趣的联系。在这篇综述中，我们总结了我们目前对小鼠中 piwi 途径的理解，该途径正在成为精子发生的基本组成部分，以确保雄性生育力和基因组完整性。
