Integrator and protein phosphatase 2A (PP2A) form a complex that dephosphorylates paused RNA polymerase II (Pol II), cleaves the nascent RNA, and terminates transcription. We report the structure of the pretermination complex containing the human Integrator-PP2A complex bound to paused Pol II. Integrator binds Pol II and the pausing factors DSIF and NELF to exclude binding of the elongation factors SPT6 and PAF1 complex. Integrator also binds the C-terminal domain of Pol II and positions PP2A to counteract Pol II phosphorylation and elongation. The Integrator endonuclease docks to the RNA exit site and opens to cleave nascent RNA about 20 nucleotides from the Pol II active site. Integrator does not bind the DNA clamps formed by Pol II and DSIF, enabling release of DNA and transcription termination.

中文翻译：

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整合子介导的转录调控的结构基础

整合子和蛋白磷酸酶 2A (PP2A) 形成一个复合物，使暂停的 RNA 聚合酶 II (Pol II) 去磷酸化，切割新生的 RNA，并终止转录。我们报告了包含人类 Integrator-PP2A 复合物的预终止复合物的结构，该复合物与暂停的 Pol II 结合。积分器结合 Pol II 和暂停因子 DSIF 和 NELF，以排除延伸因子 SPT6 和 PAF1 复合物的结合。Integrator 还结合 Pol II 的 C 末端结构域并定位 PP2A 以抵消 Pol II 磷酸化和延伸。Integrator 核酸内切酶停靠在 RNA 出口位点并打开以从 Pol II 活性位点切割约 20 个核苷酸的新生 RNA。Integrator 不结合由 Pol II 和 DSIF 形成的 DNA 夹，从而使 DNA 释放和转录终止。