Structural insights into transcriptional regulation of human RNA polymerase III
Structural insights into transcriptional regulation of human RNA polymerase III
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人类 RNA 聚合酶 III 转录调控的结构见解
DOI：
10.1038/s41594-021-00557-x
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发表时间：
2021
影响因子：
16.8
通讯作者：
Jian Wu
中科院分区：
文献类型：
--
作者：
Qianmin Wang;Shaobai Li;Futang Wan;Youwei Xu;Zhenfang Wu;Mi Cao;Pengfei Lan;Ming Lei;Jian Wu
RNA聚合酶III（Pol III）合成结构化的必需小RNA，如转移RNA、5S核糖体RNA和U6小核RNA。Pol III是最大的核RNA聚合酶，由一个保守的核心区和八个组成性调节亚基组成，但这些因子如何共同调节Pol III转录仍不清楚。在这里，我们目前的冷冻EM结构的人Pol III在载脂蛋白和延长状态，揭示了一个精心策划的运动在apo的延长过渡和一个意想不到的载脂蛋白状态，其中RPC 7亚基尾巴占据的DNA-RNA结合裂缝的Pol III，这表明RPC 7起着重要的作用，在自抑制和转录起始。这些结构还揭示了TFIIS样亚基RPC 10的校对机制，RPC 10稳定地保留了其在二级通道中的催化位置，解释了Pol III转录的高保真度。我们的工作提供了一个完整的图片Pol III转录调控的机制。
RNA polymerase III (Pol III) synthesizes structured, essential small RNAs, such as transfer RNA, 5S ribosomal RNA and U6 small nuclear RNA. Pol III, the largest nuclear RNA polymerase, is composed of a conserved core region and eight constitutive regulatory subunits, but how these factors jointly regulate Pol III transcription remains unclear. Here, we present cryo-EM structures of human Pol III in both apo and elongating states, which unveil both an orchestrated movement during the apo-to-elongating transition and an unexpected apo state in which the RPC7 subunit tail occupies the DNA–RNA-binding cleft of Pol III, suggesting that RPC7 plays important roles in both autoinhibition and transcription initiation. The structures also reveal a proofreading mechanism for the TFIIS-like subunit RPC10, which stably retains its catalytic position in the secondary channel, explaining the high fidelity of Pol III transcription. Our work provides an integrated picture of the mechanism of Pol III transcription regulation.