Evidence map›Paper›PMID 36774438›Full record

ArticleNature communications2023

The ubiquitination landscape of the influenza A virus polymerase.

Franziska Günl, Tim Krischuns, Julian A Schreiber, Lea Henschel, Marius Wahrenburg, Hannes C A Drexler, Sebastian A Leidel, Vlad Cojocaru, Guiscard Seebohm, Alexander Mellmann and 3 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
4.3field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 28 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 8 institutions in 5 countries.

Franziska GünlInstitute of Virology Muenster, University of Muenster, Muenster, Germany.ORCID 0000-0002-4841-4363
Tim KrischunsInstitute of Virology Muenster, University of Muenster, Muenster, Germany.ORCID 0000-0003-2693-4701
Julian A SchreiberInstitute for Pharmaceutical and Medicinal Chemistry, University of Muenster, Muenster, Germany.ORCID 0000-0002-3847-7539
Lea HenschelInstitute of Virology Muenster, University of Muenster, Muenster, Germany.
Marius WahrenburgInstitute of Virology Muenster, University of Muenster, Muenster, Germany.
Hannes C A DrexlerBioanalytical Mass Spectrometry, Max Planck Institute for Molecular Biomedicine, Muenster, Germany.ORCID 0000-0002-8285-0644
Sebastian A LeidelDepartment of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Bern, Switzerland.
Vlad CojocaruMax Planck Institute for Molecular Biomedicine, Muenster, Germany.ORCID 0000-0003-0886-3401
Guiscard SeebohmCellular Electrophysiology and Molecular Biology, Institute for Genetics of Heart Diseases (IfGH), Department of Cardiovascular Medicine, University Hospital Muenster, Muenster, Germany.ORCID 0000-0001-9303-5373
Alexander MellmannInterdisciplinary Center for Clinical Research (IZKF), University of Muenster, Muenster, Germany.ORCID 0000-0002-0649-5185
Martin SchwemmleInstitute of Virology, University Medical Center Freiburg, Freiburg, Germany.ORCID 0000-0002-2972-6855
Stephan LudwigInstitute of Virology Muenster, University of Muenster, Muenster, Germany.ORCID 0000-0003-4490-3052
Linda BrunotteInstitute of Virology Muenster, University of Muenster, Muenster, Germany. brunotte@uni-muenster.de.ORCID 0000-0001-8074-7400
University of Münster · DEAugenstern · DECentre National de la Recherche Scientifique · FRMax Planck Institute for Molecular Biomedicine · DEUniversity Hospital Münster · DEUniversity of Applied Sciences Utrecht · NLUniversity of Bern · CHUniversity of Freiburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

During influenza A virus (IAV) infections, viral proteins are targeted by cellular E3 ligases for modification with ubiquitin. Here, we decipher and functionally explore the ubiquitination landscape of the IAV polymerase proteins during infection of human alveolar epithelial cells by applying mass spectrometry analysis of immuno-purified K-ε-GG (di-glycyl)-remnant-bearing peptides. We have identified 59 modified lysines across the three subunits, PB2, PB1 and PA of the viral polymerase of which 17 distinctively affect mRNA transcription, vRNA replication and the generation of recombinant viruses via non-proteolytic mechanisms. Moreover, further functional and in silico analysis indicate that ubiquitination at K578 in the PB1 thumb domain is mechanistically linked to dynamic structural transitions of the viral polymerase that are required for vRNA replication. Mutations K578A and K578R differentially affect the generation of recombinant viruses by impeding cRNA and vRNA synthesis, NP binding as well as polymerase dimerization. Collectively, our results demonstrate that the ubiquitin-mediated charge neutralization at PB1-K578 disrupts the interaction to an unstructured loop in the PB2 N-terminus that is required to coordinate polymerase dimerization and facilitate vRNA replication. This provides evidence that IAV exploits the cellular ubiquitin system to modulate the activity of the viral polymerase for viral replication.

Indexed as

Influenza A virusInfluenza, HumanHumansNucleotidyltransferasesRNA, ViralTranscription, GeneticUbiquitinationUbiquitinsViral ProteinsVirus ReplicationNucleotidyltransferasesRNA, ViralUbiquitinsViral Proteins

Identifiers

PMID36774438
PMCPMC9922279
OpenAlexW4320040242

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.