Structural insights into transcriptional regulation of human RNA polymerase III

Structural insights into transcriptional regulation of human RNA polymerase III
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DOI:
10.1038/s41594-021-00557-x
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发表时间:
2021
期刊:
Nature Structural & Molecular Biology
影响因子:
--
通讯作者:
Jian Wu
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

文献摘要

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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.