The host RNA polymerase II C-terminal domain is the anchor for replication of the influenza virus genome

Abstract The current model is that the influenza virus polymerase (FluPol) binds either to host RNA polymerase II (RNAP II) or to the acidic nuclear phosphoprotein 32 (ANP32), which drives its conformation and activity towards transcription or replication of the viral genome, respectively. Here, we...

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Main Authors: Tim Krischuns, Benoît Arragain, Catherine Isel, Sylvain Paisant, Matthias Budt, Thorsten Wolff, Stephen Cusack, Nadia Naffakh
Format: Article
Language:English
Published: Nature Portfolio 2024-02-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-45205-2
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author Tim Krischuns
Benoît Arragain
Catherine Isel
Sylvain Paisant
Matthias Budt
Thorsten Wolff
Stephen Cusack
Nadia Naffakh
author_facet Tim Krischuns
Benoît Arragain
Catherine Isel
Sylvain Paisant
Matthias Budt
Thorsten Wolff
Stephen Cusack
Nadia Naffakh
author_sort Tim Krischuns
collection DOAJ
description Abstract The current model is that the influenza virus polymerase (FluPol) binds either to host RNA polymerase II (RNAP II) or to the acidic nuclear phosphoprotein 32 (ANP32), which drives its conformation and activity towards transcription or replication of the viral genome, respectively. Here, we provide evidence that the FluPol-RNAP II binding interface, beyond its well-acknowledged function in cap-snatching during transcription initiation, has also a pivotal role in replication of the viral genome. Using a combination of cell-based and in vitro approaches, we show that the RNAP II C-terminal-domain, jointly with ANP32, enhances FluPol replication activity. We observe successive conformational changes to switch from a transcriptase to a replicase conformation in the presence of the bound RNPAII C-terminal domain and propose a model in which the host RNAP II is the anchor for transcription and replication of the viral genome. Our data open new perspectives on the spatial coupling of viral transcription and replication and the coordinated balance between these two activities.
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spelling doaj.art-b3842536fde24ca59325f1c6a87e2e032024-03-05T19:42:31ZengNature PortfolioNature Communications2041-17232024-02-0115111910.1038/s41467-024-45205-2The host RNA polymerase II C-terminal domain is the anchor for replication of the influenza virus genomeTim Krischuns0Benoît Arragain1Catherine Isel2Sylvain Paisant3Matthias Budt4Thorsten Wolff5Stephen Cusack6Nadia Naffakh7Institut Pasteur, Université Paris Cité, CNRS UMR 3569, RNA Biology of Influenza VirusEuropean Molecular Biology LaboratoryInstitut Pasteur, Université Paris Cité, CNRS UMR 3569, RNA Biology of Influenza VirusInstitut Pasteur, Université Paris Cité, CNRS UMR 3569, RNA Biology of Influenza VirusUnit 17 “Influenza and other Respiratory Viruses”, Robert Koch InstitutUnit 17 “Influenza and other Respiratory Viruses”, Robert Koch InstitutEuropean Molecular Biology LaboratoryInstitut Pasteur, Université Paris Cité, CNRS UMR 3569, RNA Biology of Influenza VirusAbstract The current model is that the influenza virus polymerase (FluPol) binds either to host RNA polymerase II (RNAP II) or to the acidic nuclear phosphoprotein 32 (ANP32), which drives its conformation and activity towards transcription or replication of the viral genome, respectively. Here, we provide evidence that the FluPol-RNAP II binding interface, beyond its well-acknowledged function in cap-snatching during transcription initiation, has also a pivotal role in replication of the viral genome. Using a combination of cell-based and in vitro approaches, we show that the RNAP II C-terminal-domain, jointly with ANP32, enhances FluPol replication activity. We observe successive conformational changes to switch from a transcriptase to a replicase conformation in the presence of the bound RNPAII C-terminal domain and propose a model in which the host RNAP II is the anchor for transcription and replication of the viral genome. Our data open new perspectives on the spatial coupling of viral transcription and replication and the coordinated balance between these two activities.https://doi.org/10.1038/s41467-024-45205-2
spellingShingle Tim Krischuns
Benoît Arragain
Catherine Isel
Sylvain Paisant
Matthias Budt
Thorsten Wolff
Stephen Cusack
Nadia Naffakh
The host RNA polymerase II C-terminal domain is the anchor for replication of the influenza virus genome
Nature Communications
title The host RNA polymerase II C-terminal domain is the anchor for replication of the influenza virus genome
title_full The host RNA polymerase II C-terminal domain is the anchor for replication of the influenza virus genome
title_fullStr The host RNA polymerase II C-terminal domain is the anchor for replication of the influenza virus genome
title_full_unstemmed The host RNA polymerase II C-terminal domain is the anchor for replication of the influenza virus genome
title_short The host RNA polymerase II C-terminal domain is the anchor for replication of the influenza virus genome
title_sort host rna polymerase ii c terminal domain is the anchor for replication of the influenza virus genome
url https://doi.org/10.1038/s41467-024-45205-2
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