The RNA Polymerase II subunit RPB-9 recruits the Integrator complex to terminate C. elegans piRNA transcription

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（PIWI-interacting RNAs，以下简称piRNAs）是一类由基因组编码的小型RNA，在多种动物体内可调控生殖细胞发育并维持生殖系完整性。成熟piRNAs可与Piwi Argonaute蛋白（Piwi Argonaute proteins）结合，沉默互补转录本，其中涵盖转座元件与内源基因。piRNA的生物发生机制多样且目前仍未被充分阐明。本研究在秀丽隐杆线虫（Caenorhabditis elegans）中鉴定出RNA聚合酶II（RNA Polymerase II，简称RNA Pol II）的核心亚基RPB-9是piRNA介导的基因沉默所必需的因子。实验证实，rpb-9可启动生殖系内两类DNA转座子家族以及部分体细胞基因的可遗传piRNA介导基因沉默。本研究通过遗传与生化实验证据表明，RPB-9可在piRNA基因位点招募Integrator复合物（Integrator complex），进而促进转录终止，从而保障piRNA的生物发生。本研究最终得出结论：piRNA通路在快速进化过程中，招募并利用了一套古老的高保真转录机器。