MRC London Institute of Medical Sciences, London, UK.
Institute of Clinical Sciences, Imperial College London, London, UK.
EMBO J. 2021 Mar 1;40(5):e105564. doi: 10.15252/embj.2020105564. Epub 2020 Dec 19.
Piwi-interacting RNAs (piRNAs) play key roles in germline development and genome defence in metazoans. In C. elegans, piRNAs are transcribed from > 15,000 discrete genomic loci by RNA polymerase II (Pol II), resulting in 28 nt short-capped piRNA precursors. Here, we investigate transcription termination at piRNA loci. We show that the Integrator complex, which terminates snRNA transcription, is recruited to piRNA loci. Moreover, we demonstrate that the catalytic activity of Integrator cleaves nascent capped piRNA precursors associated with promoter-proximal Pol II, resulting in termination of transcription. Loss of Integrator activity, however, does not result in transcriptional readthrough at the majority of piRNA loci. Taken together, our results draw new parallels between snRNA and piRNA biogenesis in nematodes and provide evidence of a role for the Integrator complex as a terminator of promoter-proximal RNA polymerase II during piRNA biogenesis.
Piwi 相互作用 RNA（piRNAs）在后生动物的生殖细胞发育和基因组防御中发挥关键作用。在 C. elegans 中，piRNAs 由 RNA 聚合酶 II（Pol II）从>15000 个离散的基因组座转录而来，产生 28 个核苷酸短帽 piRNA 前体。在这里，我们研究了 piRNA 座的转录终止。我们表明，终止 snRNA 转录的整合体复合物被募集到 piRNA 座。此外，我们证明整合体的催化活性切割与启动子近端 Pol II 相关的新生 capped piRNA 前体，导致转录终止。然而，整合体活性的丧失并不会导致大多数 piRNA 座的转录通读。总之，我们的结果在线虫的 snRNA 和 piRNA 生物发生之间划出了新的相似之处，并为整合体复合物作为 piRNA 生物发生过程中启动子近端 RNA 聚合酶 II 终止子的作用提供了证据。
