Cutoff Suppresses RNA Polymerase II Termination to Ensure Expression of piRNA Precursors.
Cutoff Suppresses RNA Polymerase II Termination to Ensure Expression of piRNA Precursors.
复制标题
截止值抑制 RNA 聚合酶 II 终止，以确保 piRNA 前体的表达。
DOI：
10.1016/j.molcel.2016.05.010
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发表时间：
2016-07-07
期刊：
影响因子：
16
通讯作者：
Aravin AA
中科院分区：
文献类型：
--
作者：
Chen YA;Stuwe E;Luo Y;Ninova M;Le Thomas A;Rozhavskaya E;Li S;Vempati S;Laver JD;Patel DJ;Smibert CA;Lipshitz HD;Toth KF;Aravin AA
被称为pirna的小非编码rna作为适应性免疫系统的向导，抑制后生动物生殖细胞中的转座因子。在果蝇中，由Rhino、Deadlock和Cutoff （Cuff）组成的RDC复合物结合了双链piRNA簇的染色质，这是编码piRNA前体的特殊基因组区域。RDC复合体是piRNA前体转录所必需的，尽管其允许转录的机制尚不清楚。在这里，我们表明Cuff可以防止RNA聚合酶II的过早终止。Cuff通过干扰裂解和聚腺苷化特异性因子（CPSF）复合物的募集来阻止新生RNA在poly(A)位点的裂解。袖带还保护加工过的转录本不被核酸外切酶Rat1降解。我们的工作揭示了一个概念上不同的转录增强机制。与其他通过结合新生RNA上的特定信号来调节终止的因子不同，RDC复合物以染色质依赖和序列独立的方式抑制终止。
Small non-coding RNAs called piRNAs serve as guides for an adaptable immune system that represses transposable elements in germ cells of Metazoa. In Drosophila the RDC complex, composed of Rhino, Deadlock and Cutoff (Cuff) binds chromatin of dual-strand piRNA clusters, special genomic regions, which encode piRNA precursors. The RDC complex is required for transcription of piRNA precursors, though the mechanism by which it licenses transcription remained unknown. Here we show that Cuff prevents premature termination of RNA polymerase II. Cuff prevents cleavage of nascent RNA at poly(A) sites by interfering with recruitment of the cleavage and polyadenylation specificity factor (CPSF) complex. Cuff also protects processed transcripts from degradation by the exonuclease Rat1. Our work reveals a conceptually different mechanism of transcriptional enhancement. In contrast to other factors that regulate termination by binding to specific signals on nascent RNA, the RDC complex inhibits termination in a chromatin-dependent and sequence-independent manner.