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


Journal

The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R

Informations de publication

Date de publication:
07 2023
Historique:
received: 30 11 2022
revised: 15 05 2023
accepted: 16 05 2023
medline: 31 7 2023
pubmed: 26 5 2023
entrez: 25 5 2023
Statut: ppublish

Résumé

The TFIIF-like Rpc53/Rpc37 heterodimer of RNA polymerase (pol) III is involved in various stages of transcription. The C-terminal region of Rpc53 dimerizes with Rpc37 to anchor on the lobe domain of the pol III cleft. However, structural and functional features of the Rpc53 N-terminal region had not been characterized previously. Here, we conducted site-directed alanine replacement mutagenesis on the Rpc53 N-terminus, generating yeast strains that exhibited a cold-sensitive growth defect and severely compromised pol III transcriptional activity. Circular dichroism and NMR spectroscopy revealed a highly disordered 57-amino acid polypeptide in the Rpc53 N-terminus. This polypeptide is a versatile protein-binding module displaying nanomolar-level binding affinities for Rpc37 and the Tfc4 subunit of the transcription initiation factor TFIIIC. Accordingly, we denote this Rpc53 N-terminus polypeptide as the TFIIIC-binding region or CBR. Alanine replacements in the CBR significantly reduced its binding affinity for Tfc4, highlighting its functional importance to cell growth and transcription in vitro. Our study reveals the functional basis for Rpc53's CBR in assembly of the pol III transcription initiation complex.

Identifiants

pubmed: 37230389
pii: S0021-9258(23)01887-2
doi: 10.1016/j.jbc.2023.104859
pmc: PMC10404625
pii:
doi:

Substances chimiques

transcription factor TFIIIC 0
transcription factor TFIIF EC 3.6.4.12
RNA Polymerase III EC 2.7.7.6
Transcription Factors, TFIII 0
Peptides 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

104859

Commentaires et corrections

Type : ErratumIn

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Auteurs

Arvind Chandra Shekhar (AC)

Molecular and Cell Biology, Taiwan International Graduate Program, Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, R.O.C.; Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan, R.O.C.

Wen-Jin Wu (WJ)

Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan, R.O.C.

Hung-Ta Chen (HT)

Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan, R.O.C.. Electronic address: htchen012@gate.sinica.edu.tw.

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Classifications MeSH