Unheeded SARS-CoV-2 proteins? A deep look into negative-sense RNA.
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Authors
Bartas, Martin
Volná, Adriana
Beaudoin, Christopher A
Poulsen, Ebbe Toftgaard
Červeň, Jiří
Brázda, Václav
Špunda, Vladimír
Blundell, Tom L
Pečinka, Petr
Publication Date
2022-03-01Journal Title
Briefings in Bioinformatics
ISSN
1467-5463
Publisher
Oxford University Press (OUP)
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Bartas, M., Volná, A., Beaudoin, C. A., Poulsen, E. T., Červeň, J., Brázda, V., Špunda, V., et al. (2022). Unheeded SARS-CoV-2 proteins? A deep look into negative-sense RNA.. Briefings in Bioinformatics https://doi.org/10.1093/bib/bbac045
Abstract
SARS-CoV-2 is a novel positive-sense single-stranded RNA virus from the Coronaviridae family (genus Betacoronavirus), which has been established as causing the COVID-19 pandemic. The genome of SARS-CoV-2 is one of the largest among known RNA viruses, comprising of at least 26 known protein-coding loci. Studies thus far have outlined the coding capacity of the positive-sense strand of the SARS-CoV-2 genome, which can be used directly for protein translation. However, it has been recently shown that transcribed negative-sense viral RNA intermediates that arise during viral genome replication from positive-sense viruses can also code for proteins. No studies have yet explored the potential for negative-sense SARS-CoV-2 RNA intermediates to contain protein-coding loci. Thus, using sequence and structure-based bioinformatics methodologies, we have investigated the presence and validity of putative negative-sense ORFs (nsORFs) in the SARS-CoV-2 genome. Nine nsORFs were discovered to contain strong eukaryotic translation initiation signals and high codon adaptability scores, and several of the nsORFs were predicted to interact with RNA-binding proteins. Evolutionary conservation analyses indicated that some of the nsORFs are deeply conserved among related coronaviruses. Three-dimensional protein modeling revealed the presence of higher order folding among all putative SARS-CoV-2 nsORFs, and subsequent structural mimicry analyses suggest similarity of the nsORFs to DNA/RNA-binding proteins and proteins involved in immune signaling pathways. Altogether, these results suggest the potential existence of still undescribed SARS-CoV-2 proteins, which may play an important role in the viral lifecycle and COVID-19 pathogenesis.
Keywords
Kozak sequence, ORFs, RNA, SARS-CoV-2, proteomics, structures
Sponsorship
Wellcome Trust (200814/Z/16/Z)
Identifiers
External DOI: https://doi.org/10.1093/bib/bbac045
This record's URL: https://www.repository.cam.ac.uk/handle/1810/334788
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