tetano
Editor, Senior Moderator
Brief Bioinform
. 2022 Mar 1;bbac045.
doi: 10.1093/bib/bbac045. Online ahead of print.
Unheeded SARS-CoV-2 proteins? A deep look into negative-sense RNA
Martin Bartas[SUP] 1 [/SUP], Adriana Volná[SUP] 2 [/SUP], Christopher A Beaudoin[SUP] 3 [/SUP], Ebbe Toftgaard Poulsen[SUP] 4 [/SUP], Jiří Červeň[SUP] 1 [/SUP], Václav Brázda[SUP] 5 [/SUP], Vladimír Špunda[SUP] 2 6 [/SUP], Tom L Blundell[SUP] 3 [/SUP], Petr Pečinka[SUP] 1 [/SUP]
Affiliations
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.
. 2022 Mar 1;bbac045.
doi: 10.1093/bib/bbac045. Online ahead of print.
Unheeded SARS-CoV-2 proteins? A deep look into negative-sense RNA
Martin Bartas[SUP] 1 [/SUP], Adriana Volná[SUP] 2 [/SUP], Christopher A Beaudoin[SUP] 3 [/SUP], Ebbe Toftgaard Poulsen[SUP] 4 [/SUP], Jiří Červeň[SUP] 1 [/SUP], Václav Brázda[SUP] 5 [/SUP], Vladimír Špunda[SUP] 2 6 [/SUP], Tom L Blundell[SUP] 3 [/SUP], Petr Pečinka[SUP] 1 [/SUP]
Affiliations
- PMID: 35229157
- DOI: 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.