Unheeded SARS-CoV-2 proteins? A deep look into negative-sense RNA

0558374 - BFÚ 2023 RIV GB eng J - Článek v odborném periodiku
Bartas, M. - Volna, A. - Beaudoin, C. - Poulsen, E. - Cerven, J. - Brázda, Václav - Špunda, V. - Blundell, T. L. - Pečinka, P.
Unheeded SARS-CoV-2 proteins? A deep look into negative-sense RNA.
Briefings in Bioinformatics. Roč. 23, č. 3 (2022). ISSN 1467-5463. E-ISSN 1477-4054
Institucionální podpora: RVO:68081707
Klíčová slova: web server * visualization * translation * prediction * mechanism * helicase
Obor OECD: Cell biology
Impakt faktor: 9.5, rok: 2022
Způsob publikování: Open access s časovým embargem
https://academic.oup.com/bib/article/23/3/bbac045/6539840?login=true

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.
Trvalý link: https://hdl.handle.net/11104/0339542