Structural basis of template strand deoxyuridine promoter recognition by a viral RNA polymerase
Year: 2022
Type: article
Abstract: Recognition of promoters in bacterial RNA polymerases (RNAPs) is controlled by their sigma subunits that first bind to a double-stranded DNA element ~35 to ~14 nucleotides upstream of the transcription start site (TSS) and then capture several bases of the non-template strand ~10 nucleotides upstream of the TSS. Here, we shift this paradigm and explain the mechanism by which the phage AR9 non-virion RNAP (nvRNAP), a bacterial RNAP homolog, recognizes a −10 promoter element in the template strand directly. Together, the AR9 nvRNAP sigma-like subunit, the enzyme core, and the template strand itself form two nucleotide base-accepting pockets whose shapes dictate the AR9 nvRNAP’s deoxyuridine promoter requirement. A single amino acid substitution in the promoter specificity subunit allows one of these pockets to accept a thymine base thus expanding the enzyme’s promoter consensus. Our work demonstrates the extent to which viruses can evolve host-derived multisubunit enzymes to control host takeover.
Source: Nature Communications
Institutions: The University of Texas Medical Branch at Galveston, Skolkovo Institute of Science and Technology, Rowan University, Peter the Great St. Petersburg Polytechnic University, Google DeepMind (United Kingdom), Rutgers, The State University of New Jersey, Russian Academy of Sciences, Institute of Molecular Genetics
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,890
Funders: Howard Hughes Medical Institute, U.S. Department of Energy, Michigan Economic Development Corporation, University of Texas Medical Branch, Russian Foundation for Basic Research, Russian Science Foundation, Skolkovo Institute of Science and Technology, National Institutes of Health, Office of Science, Department of Mechanical Engineering, University of Texas at Austin, Michigan Technology Tri-Corridor, Simons Center for the Social Brain, Massachusetts Institute of Technology, National Institute of General Medical Sciences, Argonne National Laboratory, SLAC National Accelerator Laboratory
Awards: G102163711, G107546177, G1286236842, G1313983767, G1414775356, G1451874870, G1505794299, G1664757510, G1816284028, G1947107004, G2101401529, G2287611682, G262962599, G2638771445, G2887060908, G2896567508, G3075337988, G3083819904, G3329398301, G340565428, G365575497, G382641700, G416541740, G419881185, G4269941704, G42916606, G4501827968, G469876061, G4773269573, Structural and functional determinants of decision-making in bacteriophage host recognition, G498139845, G5106849484, G5607048534, G5864254528, G5906309288, G6101244626, Structural dynamics of RNAP-promoter complex in late transcription initiation, G6608191692, G6652958823, G6848031779, G6918803902, G7147508703, G7368700025, G805243471, G8361579813, G8367278906, G8764064047, G969889393, G993149817
OpenAlex ID: W4283157815