ArticleNucleic acids research2017
An in vitro fluorescence based study of initiation of RNA synthesis by influenza B polymerase.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 58 citations in OpenAlex.
- Article
- Enhanced genome replication activity of pandemic H1N1 influenza A virus through PA mutations.Journal of virology · 2026Article
- Cryo-EM structure of influenza polymerase bound to the cRNA promoter provides insights into the mechanism of viral replication.Communications biology · 2025Article
- Article
- Mutagenesis studies suggest a mechanism for influenza polymerase stalling during polyadenylation.Nucleic acids research · 2025Article
- Cryo-EM structures of Thogoto virus polymerase reveal unique RNA transcription and replication mechanisms among orthomyxoviruses.Nature communications · 2024Article
- Review
- Existing Evidence for Influenza B Virus Adaptations to Drive Replication in Humans as the Primary Host.Viruses · 2023Review
- An intermediate state allows influenza polymerase to switch smoothly between transcription and replication cycles.Nature structural & molecular biology · 2023Article
- Structural and functional characterization of the Sin Nombre virus L protein.PLoS pathogens · 2023Article
- Progression of Antiviral Agents Targeting Viral Polymerases.Molecules (Basel, Switzerland) · 2022Review
- Type B and type A influenza polymerases have evolved distinct binding interfaces to recruit the RNA polymerase II CTD.PLoS pathogens · 2022Article
- Contemporary medicinal chemistry strategies for the discovery and optimization of influenza inhibitors targeting vRNP constituent proteins.Acta pharmaceutica Sinica. B · 2022Review
- A novel mechanism of enhanced transcription activity and fidelity for influenza A viral RNA-dependent RNA polymerase.Nucleic acids research · 2021Article
- Structure and Function of Influenza Polymerase.Cold Spring Harbor perspectives in medicine · 2021Review
- Substrate inhibition by the blockage of product release and its control by tunnel engineering.RSC chemical biology · 2021Article
- Application of weighted gene co-expression network analysis to identify the hub genes in H1N1.International journal of physiology, pathophysiology and pharmacology · 2021Article
- Phosphorylation controls RNA binding and transcription by the influenza virus polymerase.PLoS pathogens · 2020Article
- Mutation of an Influenza Virus Polymerase 3' RNA Promoter Binding Site Inhibits Transcription Elongation.Journal of virology · 2020Article
- Elucidating the Interactions between Influenza Virus Polymerase and Host Factor ANP32A.Journal of virology · 2020Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
Influenza polymerase replicates, via a complementary RNA intermediate (cRNA), and transcribes the eight viral RNA (vRNA) genome segments. To initiate RNA synthesis it is bound to the conserved 5΄ and 3΄ extremities of the vRNA or cRNA (the 'promoter'). 5΄-3΄ base-pairing in the distal promoter region is essential to position the template RNA at the polymerase active site, as shown by a new crystal structure with the 3΄ end threading through the template entry tunnel. We develop fluorescence polarization assays to quantify initiation of cap-primed (transcription) or unprimed (replication) RNA synthesis by recombinant influenza B polymerase bound to the vRNA or cRNA promoter. The rate-limiting step is formation of a primed initiation complex with minimally ApG required to stabilize the 3΄ end of the template within the active-site. Polymerase bound to the vRNA promoter initiates RNA synthesis terminally, while the cRNA promoter directs internal initiation at a significantly lower rate. Progression to elongation requires breaking the promoter 5΄-3΄ base-pairing region and favourable compensation by the emerging template-product base-pairs. The RNA synthesis assay is adaptable to high-throughput screening for polymerase inhibitors. In a pilot study, we find that initiation at the cRNA promoter is unusually susceptible to inhibition by 2΄F-2΄dNTPs.
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Registered trials
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.