ArticlePLoS pathogens2017
RNA elongation by respiratory syncytial virus polymerase is calibrated by conserved region V.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 44 citations in OpenAlex.
- mRNA cap formation by the human respiratory syncytial virus large protein.Nucleic acids research · 2026Article
- Catching our breath: development of interventions and therapies for respiratory syncytial virus.Microbiology and molecular biology reviews : MMBR · 2026Review
- Functional minigenome system reveals polymerase features of swine orthopneumovirus.Journal of virology · 2026Article
- Human metapneumovirus: understanding the molecular mechanisms and pathology of infection.Journal of virology · 2025Review
- Review
- Structural insights into the dynamic mechanism of bornavirus polymerase.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Minigenome System to Study Respiratory Syncytial Virus Transcription Versus Genome Replication.Methods in molecular biology (Clifton, N.J.) · 2025Article
- In Vitro Biochemical Assays to Study Respiratory Syncytial Virus Polymerase Activities.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Cryo-EM structure of Nipah virus RNA polymerase complex.Science advances · 2024Article
- How does the polymerase of non-segmented negative strand RNA viruses commit to transcription or genome replication?Journal of virology · 2024Review
- Article
- The cryoEM structure of the Hendra henipavirus nucleoprotein reveals insights into paramyxoviral nucleocapsid architectures.Scientific reports · 2024Article
- Structural basis for dimerization of a paramyxovirus polymerase complex.Nature communications · 2024Article
- Structural and mechanistic insights into the inhibition of respiratory syncytial virus polymerase by a non-nucleoside inhibitor.Communications biology · 2023Article
- Conserved allosteric inhibitory site on the respiratory syncytial virus and human metapneumovirus RNA-dependent RNA polymerases.Communications biology · 2023Article
- Biochemistry of the Respiratory Syncytial Virus L Protein Embedding RNA Polymerase and Capping Activities.Viruses · 2023Review
- Orally efficacious lead of the AVG inhibitor series targeting a dynamic interface in the respiratory syncytial virus polymerase.Science advances · 2022Article
- Distinctive features of the respiratory syncytial virus priming loop compared to other non-segmented negative strand RNA viruses.PLoS pathogens · 2022Article
- GDP polyribonucleotidyltransferase domain of vesicular stomatitis virus polymerase regulates leader-promoter escape and polyadenylation-coupled termination during stop-start transcription.PLoS pathogens · 2022Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The large polymerase subunit (L) of non-segmented negative strand RNA viruses transcribes viral mRNAs and replicates the viral genome. Studies with VSV have shown that conserved region V (CRV) of the L protein is part of the capping domain. However, CRV folds over and protrudes into the polymerization domain, suggesting that it might also have a role in RNA synthesis. In this study, the role of respiratory syncytial virus (RSV) CRV was evaluated using single amino acid substitutions and a small molecule inhibitor called BI-D. Effects were analyzed using cell-based minigenome and in vitro biochemical assays. Several amino acid substitutions inhibited production of capped, full-length mRNA and instead resulted in accumulation of short transcripts of approximately 40 nucleotides in length, confirming that RSV CRV has a role in capping. In addition, all six variants tested were either partially or completely defective in RNA replication. This was due to an inability of the polymerase to efficiently elongate the RNA within the promoter region. BI-D also inhibited transcription and replication. In this case, polymerase elongation activity within the promoter region was enhanced, such that the small RNA transcribed from the promoter was not released and instead was elongated past the first gene start signal. This was accompanied by a decrease in mRNA initiation at the first gene start signal and accumulation of aberrant RNAs of varying length. Thus, in addition to its function in mRNA capping, conserved region V modulates the elongation properties of the polymerase to enable productive transcription and replication to occur.
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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.