Structural Insights into Transcriptional Regulation of Human RNA Polymerase III

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2021 Feb 9

PMID 33558766

Citations 23

Authors

Qianmin Wang

Shaobai Li

Futang Wan

Youwei Xu

Zhenfang Wu

Mi Cao

Pengfei Lan

Ming Lei

Jian Wu

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

A Combinatorial Regulatory Platform Determines Expression of RNA Polymerase III Subunit RPC7α () in Cancer.

Cheng R, Zhou S, K C R, Lizarazo S, Mouli L, Jayanth A Cancers (Basel). 2023; 15(20.

PMID: 37894362 PMC: 10605170. DOI: 10.3390/cancers15204995.

Mutational and biophysical analyses reveal a TFIIIC binding region in the TFIIF-related Rpc53 subunit of RNA polymerase III.

Chandra Shekhar A, Wu W, Chen H J Biol Chem. 2023; 299(7):104859.

PMID: 37230389 PMC: 10404625. DOI: 10.1016/j.jbc.2023.104859.

Structural basis of Ty1 integrase tethering to RNA polymerase III for targeted retrotransposon integration.

Nguyen P, Huecas S, Asif-Laidin A, Plaza-Pegueroles A, Capuzzi B, Palmic N Nat Commun. 2023; 14(1):1729.

PMID: 36977686 PMC: 10050235. DOI: 10.1038/s41467-023-37109-4.

ThrRS-Mediated Translation Regulation of the RNA Polymerase III Subunit RPC10 Occurs through an Element with Similarity to Cognate tRNA ASL and Affects tRNA Levels.

Levi O, Mallik M, Arava Y Genes (Basel). 2023; 14(2).

PMID: 36833389 PMC: 9956033. DOI: 10.3390/genes14020462.

Regulation of ribosomal RNA gene copy number, transcription and nucleolus organization in eukaryotes.

Hori Y, Engel C, Kobayashi T Nat Rev Mol Cell Biol. 2023; 24(6):414-429.

PMID: 36732602 DOI: 10.1038/s41580-022-00573-9.

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