The Living Systems Institute, University of Exeter, Stocker Rd, Exeter EX4 4QD, UK.
The Living Systems Institute, University of Exeter, Stocker Rd, Exeter EX4 4QD, UK.
Cell Rep. 2020 Oct 27;33(4):108319. doi: 10.1016/j.celrep.2020.108319.
Many RNA polymerases terminate transcription using allosteric/intrinsic mechanisms, whereby protein alterations or nucleotide sequences promote their release from DNA. RNA polymerase II (Pol II) is somewhat different based on its behavior at protein-coding genes where termination additionally requires endoribonucleolytic cleavage and subsequent 5'→3' exoribonuclease activity. The Pol-II-transcribed small nuclear RNAs (snRNAs) also undergo endoribonucleolytic cleavage by the Integrator complex, which promotes their transcriptional termination. Here, we confirm the involvement of Integrator but show that Integrator-independent processes can terminate snRNA transcription both in its absence and naturally. This is often associated with exosome degradation of snRNA precursors that long-read sequencing analysis reveals as frequently terminating at T-runs located downstream of some snRNAs. This finding suggests a unifying vulnerability of RNA polymerases to such sequences given their well-known roles in terminating Pol III and bacterial RNA polymerase.
许多 RNA 聚合酶使用变构/内在机制终止转录，其中蛋白质改变或核苷酸序列促进它们从 DNA 上释放。基于其在蛋白质编码基因上的行为，RNA 聚合酶 II（Pol II）略有不同，终止还需要内切核酸酶切割和随后的 5'→3'外切核酸酶活性。Pol-II 转录的小核 RNA（snRNA）也被整合体复合物进行内切核酸酶切割，这促进了它们的转录终止。在这里，我们证实了整合体的参与，但表明整合体独立的过程可以在其缺失和自然状态下终止 snRNA 的转录。这通常与 exosome 降解 snRNA 前体有关，长读测序分析显示，这些 snRNA 前体通常在一些 snRNA 下游的 T 序列处终止。这一发现表明，鉴于其在终止 Pol III 和细菌 RNA 聚合酶中的已知作用，RNA 聚合酶对这些序列具有普遍的脆弱性。
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