Unheeded SARS-CoV-2 proteins? A deep look into negative-sense RNA.
Beaudoin, Christopher A
Poulsen, Ebbe Toftgaard
Blundell, Tom L
Briefings in Bioinformatics
Oxford University Press (OUP)
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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
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.
Kozak sequence, ORFs, RNA, SARS-CoV-2, proteomics, structures
Wellcome Trust (200814/Z/16/Z)
External DOI: https://doi.org/10.1093/bib/bbac045
This record's URL: https://www.repository.cam.ac.uk/handle/1810/334788
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/