Structural insights into influenza A virus ribonucleoproteins reveal a processive helical track as transcription mechanism.


Journal

Nature microbiology
ISSN: 2058-5276
Titre abrégé: Nat Microbiol
Pays: England
ID NLM: 101674869

Informations de publication

Date de publication:
05 2020
Historique:
received: 19 10 2018
accepted: 24 01 2020
pubmed: 11 3 2020
medline: 28 7 2020
entrez: 11 3 2020
Statut: ppublish

Résumé

The influenza virus genome consists of eight viral ribonucleoproteins (vRNPs), each consisting of a copy of the polymerase, one of the genomic RNA segments and multiple copies of the nucleoprotein arranged in a double helical conformation. vRNPs are macromolecular machines responsible for messenger RNA synthesis and genome replication, that is, the formation of progeny vRNPs. Here, we describe the structural basis of the transcription process. The mechanism, which we call the 'processive helical track', is based on the extreme flexibility of the helical part of the vRNP that permits a sliding movement between both antiparallel nucleoprotein-RNA strands, thereby allowing the polymerase to move over the genome while bound to both RNA ends. Accordingly, we demonstrate that blocking this movement leads to inhibition of vRNP transcriptional activity. This mechanism also reveals a critical role of the nucleoprotein in maintaining the double helical structure throughout the copying process to make the RNA template accessible to the polymerase.

Identifiants

pubmed: 32152587
doi: 10.1038/s41564-020-0675-3
pii: 10.1038/s41564-020-0675-3
doi:

Substances chimiques

Nucleoproteins 0
RNA, Viral 0
Ribonucleoproteins 0
Viral Proteins 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

727-734

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Auteurs

Rocío Coloma (R)

Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.

Rocío Arranz (R)

Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.

José M de la Rosa-Trevín (JM)

Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
Department of Biochemistry and Biophysics, Science for Life Laboratory, Stockholm University, Stockholm, Sweden.

Carlos O S Sorzano (COS)

Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.

Sandie Munier (S)

Unité de Génétique Moléculaire des Virus à ARN, Département de Virologie, Institut Pasteur, Paris, France.
Centre National de la Recherche Scientifique, Unité Mixte de Recherche 3569, Paris, France.
Université Paris Diderot, Sorbonne Paris Cité, Paris, France.

Diego Carlero (D)

Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.

Nadia Naffakh (N)

Unité de Génétique Moléculaire des Virus à ARN, Département de Virologie, Institut Pasteur, Paris, France.
Centre National de la Recherche Scientifique, Unité Mixte de Recherche 3569, Paris, France.
Université Paris Diderot, Sorbonne Paris Cité, Paris, France.

Juan Ortín (J)

Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain. ortinmonton@hotmail.com.

Jaime Martín-Benito (J)

Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain. jmartinb@cnb.csic.es.

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