The transition of RNA polymerase II (Pol II) from initiation to productive elongation is a central, regulated step in metazoan gene expression. At many genes, Pol II pauses stably in early elongation, remaining engaged with the 25- to 60-nt-long nascent RNA for many minutes while awaiting signals for release into the gene body. However, 15%-20% of genes display highly unstable promoter Pol II, suggesting that paused polymerase might dissociate from template DNA at these promoters and release a short, non-productive mRNA. Here, we report that paused Pol II can be actively destabilized by the Integrator complex. Specifically, we present evidence that Integrator utilizes its RNA endonuclease activity to cleave nascent RNA and drive termination of paused Pol II. These findings uncover a previously unappreciated mechanism of metazoan gene repression, akin to bacterial transcription attenuation, wherein promoter-proximal Pol II is prevented from entering productive elongation through factor-regulated termination.

中文翻译：

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整合体复合物在蛋白质编码基因处减弱启动子近端转录。

RNA聚合酶II（Pol II）从起始到有效延伸的转变是后生动物基因表达中一个重要的调控步骤。在许多基因上，Pol II在早期延伸中稳定停顿，在等待释放到基因体内的信号之前，与25至60 nt长的新生RNA保持接合数分钟。但是，有15％-20％的基因显示出高度不稳定的启动子Pol II，这表明暂停的聚合酶可能会在这些启动子处从模板DNA上解离，并释放出短的非生产性mRNA。在这里，我们报告暂停的Pol II可能会因Integrator复合系统而受到破坏。具体来说，我们目前提供的证据表明Integrator利用其RNA内切核酸酶活性来裂解新生的RNA并驱动终止的Pol II终止。这些发现揭示了后生动物基因抑制的先前未知的机制，