Identification of DEDD- and PHP-Superfamilies of Proofreading Exonucleases in the Acidic Protein Subunit PA of RNA Polymerase of Human Influenza Viruses
Department of Molecular Microbiology, School of Biotechnology, Madurai Kamaraj University, Madurai – 625 021, India.
Research Article
World Journal of Advanced Research and Reviews, 2022, 16(02), 804-824
Publication history:
Received on 12 October 2022; revised on 19 November 2022; accepted on 21 November 2022
Abstract:
RNA polymerase from human influenza viruses A, B and C is a heterotrimric enzyme, made up of three different subunits. It performs the crucial function of both genome replication as well as transcription. One of the RNA polymerase subunits, the polymerase acidic protein subunit (PA), is suggested to function as an endonuclease in a ‘cap-snatching’ mechanism, unique to influenza viruses. However, by multiple sequence alignment (MSA) analysis, it was found that the PA subunits of the polymerases do harbour typical proofreading (PR) DEDD-superfamily of exonuclease active site in all three viruses. However, in human influenza A virus, an additional putative PR exonuclease active site amino acids belonging to Polymerase-Histidinol Phosphatase (PHP)-superfamily are identified. The identified active site amino acids data are in close agreement with the similar DEDD- and PHP-superfamilies of PR exonucleases, already reported from both DNA-dependent RNA polymerases (DdRps) and RNA-dependent RNA polymerases (RdRps) from prokaryotes, eukaryotes and RNA viruses. The putative PHP–family PR exonuclease active site, identified by MSA analysis, is also in close agreement to the already reported PHP–family of PR exonuclease active sites from DdDps of replicases and pol X polymerases of the bacterial kingdom. Only in the pandemic causing human influenza A virus, the putative PHP-family PR exonuclease domain is found along with the DEDD-family PR exonuclease domain.
Keywords:
Human Influenza Viruses; RNA Polymerase; Polymerase Acidic Protein Subunit; Proofreading Exonucleases; DEDD-superfamily Exonucleases; PHP-superfamily Exonucleases; Active site structures
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