A comparative analysis is presented of 24 known amino acid sequences of RNA-dependent RNA polymerases of positive strand RNA viruses infecting animals, plants and bacteria. Using a newly proposed methodology of group alignment for weakly similar sequences, evolutionary conserved fragments of all these proteins were unambiguously aligned. A unique pattern (consensus) of 7 invariant amino acid residues was revealed which is absent from the sequences of other RNA and DNA polymerases and is thought to unequivocally identify the RNA-dependent RNA polymerases of positive strand RNA viruses. Based on the obtained alignment a tentative phylogenetic tree of viral RNA polymerases was constructed for the first time. The RNA-dependent RNA polymerases of positive strand RNA viruses are concluded to comprise a distinct family of evolutionary related proteins.
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J Immunother Cancer
January 2025
Division of Infection, Immunity and Respiratory Medicine, The University of Manchester, Manchester, UK
Background: Programmed cell death 1 (PD-1) signaling blockade by immune checkpoint inhibitors (ICI) effectively restores immune surveillance to treat melanoma. However, chronic interferon-gamma (IFNγ)-induced immune homeostatic responses in melanoma cells contribute to immune evasion and acquired resistance to ICI. Poly ADP ribosyl polymerase 14 (PARP14), an IFNγ-responsive gene product, partially mediates IFNγ-driven resistance.
View Article and Find Full Text PDFMol Biol Rep
January 2025
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, People's Republic of China.
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December 2024
National Research Centre "Kurchatov Institute", Moscow, 123182, Russia.
Bacterial and viral RNA polymerases are promising targets for the development of new transcription inhibitors. One of the potential blockers of RNA synthesis is 7,8-dihydro-8-oxo-1,-ethenoadenine (oxo-εA), a synthetic compound that combines two adenine modifications: 8-oxoadenine and 1,-ethenoadenine. In this study, we synthesized oxo-εA triphosphate (oxo-εATP) and showed that it could be incorporated by the RNA-dependent RNA polymerase of SARS-CoV-2 into synthesized RNA opposite template residues A and G in the presence of Mn ions.
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December 2024
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090, Russia.
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View Article and Find Full Text PDFViruses
December 2024
Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
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