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Cited by 32Influenza Virus Research StudiesVirology and Viral DiseasesViral Infectious Diseases and Gene Expression in Insects

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Phosphorylation controls RNA binding and transcription by the influenza virus polymerase

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Dawson, Anthony R., Wilson, Gary M., Freiberger, Elyse C., Mondal, Arindam, Coon, Joshua J., Mehle, Andrew·2020·PLOS Pathogens
DOI 10.1371/journal.ppat.1008841PMC PMC7494117

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Abstract

The influenza virus polymerase transcribes and replicates the viral genome. The proper timing and balance of polymerase activity is important for successful replication. Genome replication is controlled in part by phosphorylation of NP that regulates assembly of the replication machinery. However, it remains unclear whether phosphorylation directly regulated polymerase activity. Here we identified polymerase phosphosites that control its function. Mutating phosphosites in the catalytic subunit PB1 altered polymerase activity and virus replication. Biochemical analyses revealed phosphorylation events that disrupted global polymerase function by blocking the NTP entry channel or preventing RNA binding. We also identified a regulatory site that split polymerase function by specifically suppressing transcription. These experiments show that host kinases phospho-regulate viral RNA synthesis directly by modulating polymerase activity and indirectly by controlling assembly of replication machinery. Further, they suggest polymerase phosphorylation may bias replication versus transcription at discrete times or locations during the infectious cycle.

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Metadata

Authors
Dawson, A. R., Wilson, G. M., Freiberger, E. C., Mondal, A., Coon, J. J., & Mehle, A.
Affiliations
University of Wisconsin–Madison (US)
Corresponding author
Mehle, Andrew
ORCID
Venue
PLOS Pathogens
Publisher
Public Library of Science (PLoS)
Published
2020-09-03
Volume
16
Issue
9
Pages
e1008841
ISSN
  • 1553-7366 (ISSN-L)
  • 1553-7374
DOI
10.1371/journal.ppat.1008841
PMC
PMC7494117
OpenAlex
W3083493094
Cited by
32
References
2
Citations by year
2026: 4 · 2025: 9 · 2024: 4 · 2023: 9 · 2022: 3 · 2021: 3
FWCI
2.69
Type
journal article
Language
en
Update notices
new_version (2020-09-16)
Open access
Licence
Locations
  • PLoS Pathogens (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institute of Allergy and Infectious Diseases (R01AI125271, T32AI078985)
  • National Institute of General Medical Sciences (R35GM118110, T32GM008349)
  • Burroughs Wellcome Fund (Investigator in the Pathogenesis of Disease)
Topics
  • Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
  • Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
Keywords
protein phosphorylation, phosphosites, RNA binding, viral transcription, viral genome replication
MeSH terms
A549 Cells, Animals, Dogs, Humans, Influenza A virus, Phosphorylation, RNA, Viral, Transcription, Genetic, Viral Proteins, Virus Replication, HEK293 Cells, Madin Darby Canine Kidney Cells

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