ArticleNature2017
Structural basis of an essential interaction between influenza polymerase and Pol II CTD.
Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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Who cites it
89 citing papers in PubMed, 134 citations in OpenAlex.
- Preclinical characterization of HEC116094, an oral inhibitor of the influenza A virus polymerase PB2 subunit.Emerging microbes & infections · 2026Article
- Divergent pathogenic mechanisms of influenza A and influenza B viruses.Archives of microbiology · 2026Review
- A Structural View of Influenza Virus Ribonucleoprotein Complex and Its Functions.Microorganisms · 2026Review
- Kaposi's Sarcoma-associated herpesvirus uses a novel protein fold to hijack RNA Polymerase II for viral late gene transcription.bioRxiv : the preprint server for biology · 2026Article
- Article
- Cryo-EM structure of influenza polymerase bound to the cRNA promoter provides insights into the mechanism of viral replication.Communications biology · 2025Article
- Coupling of polymerase-nucleoprotein-RNA in an influenza virus mini ribonucleoprotein complex.Nature communications · 2025Article
- Continuous evolution of Eurasian avian-like H1N1 swine influenza viruses with pdm/09-derived internal genes enhances pathogenicity in mice.Journal of virology · 2025Article
- The 5'-end segment-specific noncoding region of influenza A virus regulates both competitive multi-segment RNA transcription and selective genome packaging during infection.Journal of virology · 2025Article
- CRISPR with Transcriptional Readout reveals influenza transcription is modulated by NELF and can precipitate an interferon response.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- CRISPR with Transcriptional Readout reveals influenza transcription is modulated by NELF and can precipitate an interferon response.bioRxiv : the preprint server for biology · 2025Article
- Influenza A virus RNA localisation and the interceding trafficking pathways of the host cell.PLoS pathogens · 2025Review
- Analysis of NS2-dependent effects on influenza PB1 segment extends replication requirements beyond the canonical promoter.Nature communications · 2025Article
- LDC000067, a CDK9 inhibitor, unveils promising results in suppressing influenza virus infectionsAntimicrobial agents and chemotherapy · 2025Article
- Purification and Ultramicroscopic Observation of the Influenza A Virus Ribonucleoprotein Complex.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Emerging threats of H5N1 clade 2.3.4.4b: cross-species transmission, pathogenesis, and pandemic risk.Frontiers in cellular and infection microbiology · 2025Review
- NS2 induces an influenza A RNA polymerase hexamer and acts as a transcription to replication switch.EMBO reports · 2024Article
- Structures of influenza A and B replication complexes give insight into avian to human host adaptation and reveal a role of ANP32 as an electrostatic chaperone for the apo-polymerase.Nature communications · 2024Article
- Conformational Dynamics of Influenza A Virus Ribonucleoprotein Complexes during RNA Synthesis.ACS nano · 2024Article
- The RBPome of influenza A virus NP-mRNA reveals a role for TDP-43 in viral replication.Nucleic acids research · 2024Article
29 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The heterotrimeric influenza polymerase (FluPol), comprising subunits PA, PB1 and PB2, binds to the conserved 5' and 3' termini (the 'promoter') of each of the eight single-stranded viral RNA (vRNA) genome segments and performs both transcription and replication of vRNA in the infected cell nucleus. To transcribe viral mRNAs, FluPol associates with cellular RNA polymerase II (Pol II), which enables it to take 5'-capped primers from nascent Pol II transcripts. Here we present a co-crystal structure of bat influenza A polymerase bound to a Pol II C-terminal domain (CTD) peptide mimic, which shows two distinct phosphoserine-5 (SeP5)-binding sites in the polymerase PA subunit, accommodating four CTD heptad repeats overall. Mutagenesis of the SeP5-contacting basic residues (PA K289, R454, K635 and R638) weakens CTD repeat binding in vitro without affecting the intrinsic cap-primed (transcription) or unprimed (replication) RNA synthesis activity of recombinant polymerase, whereas in cell-based minigenome assays the same mutations substantially reduce overall polymerase activity. Only recombinant viruses with a single mutation in one of the SeP5-binding sites can be rescued, but these viruses are severely attenuated and genetically unstable. Several previously described mutants that modulate virulence can be rationalized by our results, including a second site mutation (PA(C453R)) that enables the highly attenuated mutant virus (PA(R638A)) to revert to near wild-type infectivity. We conclude that direct binding of FluPol to the SeP5 Pol II CTD is fine-tuned to allow efficient viral transcription and propose that the CTD-binding site on FluPol could be targeted for antiviral drug development.
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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.