Structural basis of template strand deoxyuridine promoter recognition by a viral RNA polymerase
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Abstract
Recognition of promoters in bacterial RNA polymerases (RNAPs) is controlled by sigma subunits. The key sequence motif recognized by the sigma, the −10 promoter element, is located in the non-template strand of the double-stranded DNA molecule ~10 nucleotides upstream of the transcription start site. Here, we explain the mechanism by which the phage AR9 non-virion RNAP (nvRNAP), a bacterial RNAP homolog, recognizes the −10 element of its deoxyuridine-containing promoter in the template strand. The AR9 sigma-like subunit, the nvRNAP enzyme core, and the template strand together form two nucleotide base-accepting pockets whose shapes dictate the requirement for the conserved deoxyuridines. A single amino acid substitution in the AR9 sigma-like subunit allows one of these pockets to accept a thymine thus expanding the promoter consensus. Our work demonstrates the extent to which viruses can evolve host-derived multisubunit enzymes to make transcription of their own genes independent of the host.
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- Authors
- Fraser, A., Sokolova, M. L., Drobysheva, A. V., Gordeeva, J. V., Borukhov, S., Jumper, J., Severinov, K. V., & Leiman, P. G.
- Affiliations
- The University of Texas Medical Branch at Galveston (US)
- Skolkovo Institute of Science and Technology (RU)
- Rowan University (US)
- Rutgers, The State University of New Jersey (US)
- Corresponding author
- Sokolova, Maria L.
- Severinov, Konstantin V.
- Leiman, Petr G.
- ORCID
- Venue
- Nature Communications
- Published
- 2022-06-20
- Volume
- 13
- Issue
- 1
- Pages
- 3526-3526
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC9209446
- OpenAlex
- W4283157815
- Cited by
- 7
- References
- 87
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 1
- FWCI
- 0.91
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- Research Square (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- University of Texas Medical Branch
- UTMB Sealy Center for Structural Biology and Molecular Biophysics
- Russian Science Foundation (19-74-00011)
- Skolkovo Institute of Science and Technology
- Russian Foundation for Basic Research (20-34-90079)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- sigma factor, promoter identification, deoxyuridine, template strand, transcription initiation
- MeSH terms
- Viral Replicase Complex Proteins, Deoxyuridine, Promoter Regions, Genetic, DNA-Directed RNA Polymerases, RNA, Viral, Sigma Factor, Transcription, Genetic
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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