Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, UK.
Department of Genetics, University of Cambridge, Cambridge, UK.
EMBO J. 2021 Mar 1;40(5):e105565. doi: 10.15252/embj.2020105565. Epub 2021 Feb 3.
PIWI-interacting RNAs (piRNAs) are genome-encoded small RNAs that regulate germ cell development and maintain germline integrity in many animals. Mature piRNAs engage Piwi Argonaute proteins to silence complementary transcripts, including transposable elements and endogenous genes. piRNA biogenesis mechanisms are diverse and remain poorly understood. Here, we identify the RNA polymerase II (RNA Pol II) core subunit RPB-9 as required for piRNA-mediated silencing in the nematode Caenorhabditis elegans. We show that rpb-9 initiates heritable piRNA-mediated gene silencing at two DNA transposon families and at a subset of somatic genes in the germline. We provide genetic and biochemical evidence that RPB-9 is required for piRNA biogenesis by recruiting the Integrator complex at piRNA genes, hence promoting transcriptional termination. We conclude that, as a part of its rapid evolution, the piRNA pathway has co-opted an ancient machinery for high-fidelity transcription.
PIWI 相互作用 RNA（piRNAs）是一类基因组编码的小 RNA，它们在许多动物中调节生殖细胞的发育并维持生殖系的完整性。成熟的 piRNA 与 Piwi Argonaute 蛋白结合，沉默互补的转录本，包括转座元件和内源性基因。piRNA 的生物发生机制多种多样，目前仍知之甚少。在这里，我们鉴定出 RNA 聚合酶 II（RNA Pol II）核心亚基 RPB-9 是线虫秀丽隐杆线虫中 piRNA 介导沉默所必需的。我们表明，rpb-9 在两个 DNA 转座子家族和生殖系中一部分体细胞基因起始了可遗传的 piRNA 介导的基因沉默。我们提供遗传和生化证据表明，RPB-9 通过在 piRNA 基因上募集整合子复合物来促进转录终止，从而需要 piRNA 的生物发生。我们的结论是，作为其快速进化的一部分，piRNA 途径已经共同采用了一种用于高保真转录的古老机制。
