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Title: Structural basis of template strand deoxyuridine promoter recognition by a viral RNA polymerase

Journal Article · · Nature Communications
 [1]; ORCiD logo [2];  [3];  [3]; ORCiD logo [4]; ORCiD logo [5]; ORCiD logo [6]; ORCiD logo [1]
  1. University of Texas Medical Branch, Galveston, TX (United States)
  2. University of Texas Medical Branch, Galveston, TX (United States); Skolkovo Institute of Science and Technology (Russian Federation)
  3. Skolkovo Institute of Science and Technology (Russian Federation)
  4. Rowan University School of Osteopathic Medicine, Stratford, NJ (United States)
  5. DeepMind Technologies Limited, London (United Kingdom)
  6. Skolkovo Institute of Science and Technology (Russian Federation); Russian Academy of Sciences (RAS), Moscow (Russian Federation); State University of New Jersey, Piscataway, NJ (United States)

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.

Research Organization:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC); Russian Science Foundation; Russian Foundation for Basic Research; Ministry of Science and Higher Education of Russian Federation; Michigan Economic Development Corporation; Michigan Technology Tri-Corridor
Grant/Contract Number:
AC02-06CH11357; AC02-05CH11231; 19-74-00011; 20-34-90079; 075-10-2021-114; 085P1000817
OSTI ID:
1875162
Alternate ID(s):
OSTI ID: 1876079
Journal Information:
Nature Communications, Vol. 13, Issue 1; ISSN 2041-1723
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
ENGLISH

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