Architecture of the yeast Pol III pre-termination complex and pausing mechanism on poly(dT) termination signals.

Cryoelectron Microscopy Poly T RNA Polymerase III / genetics Saccharomyces cerevisiae / metabolism Saccharomyces cerevisiae Proteins / metabolism Terminator Regions, Genetic
CP: Molecular biology NT strand RNA polymerase III cryo-EM pausing poly(dT) signal pre-termination complex structure-function studies termination transcription

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
06 09 2022
Historique:
received: 10 03 2022
revised: 01 07 2022
accepted: 15 08 2022
entrez: 7 9 2022
pubmed: 8 9 2022
medline: 11 9 2022
Statut: ppublish

Résumé

RNA polymerase (Pol) III is specialized to transcribe short, abundant RNAs, for which it terminates transcription on polythymine (dT) stretches on the non-template (NT) strand. When Pol III reaches the termination signal, it pauses and forms the pre-termination complex (PTC). Here, we report cryoelectron microscopy (cryo-EM) structures of the yeast Pol III PTC and complementary functional states at resolutions of 2.7-3.9 Å. Pol III recognizes the poly(dT) termination signal with subunit C128 that forms a hydrogen-bond network with the NT strand and, thereby, induces pausing. Mutating key interacting residues interferes with transcription termination in vitro, impairs yeast growth, and causes global termination defects in vivo, confirming our structural results. Additional cryo-EM analysis reveals that C53-C37, a Pol III subcomplex and key termination factor, participates indirectly in Pol III termination. We propose a mechanistic model of Pol III transcription termination and rationalize why Pol III, unlike Pol I and Pol II, terminates on poly(dT) signals.

Identifiants

DOI: 10.1016/j.celrep.2022.111316 PMID: 36070694
pubmed: 36070694
pii: S2211-1247(22)01140-8
doi: 10.1016/j.celrep.2022.111316
pii:
doi:

Substances chimiques

Saccharomyces cerevisiae Proteins 0
Poly T 25086-81-1
RNA Polymerase III EC 2.7.7.6

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

111316

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Mathias Girbig (M)

Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstraße 1, 69117 Heidelberg, Germany.

Juanjuan Xie (J)

Université de Paris, CNRS, Institut Jacques Monod, 75006 Paris, France.

Helga Grötsch (H)

Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstraße 1, 69117 Heidelberg, Germany.

Domenico Libri (D)

Université de Paris, CNRS, Institut Jacques Monod, 75006 Paris, France.

Odil Porrua (O)

Université de Paris, CNRS, Institut Jacques Monod, 75006 Paris, France.

Christoph W Müller (CW)

Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstraße 1, 69117 Heidelberg, Germany. Electronic address: christoph.mueller@embl.de.

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Classifications MeSH

questionsmedicales.fr › Techniques d'investigation › Microscopie électronique › Cryomicroscopie électronique › Architecture of the yeast Pol III...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Nucléotides › Polynucléotides › Polydésoxyribonucléotides › Poly T › Architecture of the yeast Pol III...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Phosphotransferases › Nucleotidyltransferases › RNA nucleotidyltransferases › DNA-directed RNA polymerases › RNA polymerase III › Architecture of the yeast Pol III...
questionsmedicales.fr › Eucaryotes › Champignons › Levures › Saccharomyces › Saccharomyces cerevisiae › Architecture of the yeast Pol III...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines fongiques › Protéines de Saccharomyces cerevisiae › Architecture of the yeast Pol III...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Composants de gène › Éléments de régulation transcriptionnelle › Régions terminatrices (génétique) › Architecture of the yeast Pol III...