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dc.contributor.authorPostnikova, Olga A.
dc.contributor.authorUppal, Sheetal
dc.contributor.authorHuang, Weiliang
dc.contributor.authorKane, Maureen A.
dc.contributor.authorVillasmil, Rafael
dc.contributor.authorRogozin, Igor B.
dc.contributor.authorPoliakov, Eugenia
dc.contributor.authorRedmond, T. Michael
dc.date.accessioned2021-06-24T17:31:43Z
dc.date.available2021-06-24T17:31:43Z
dc.date.issued2021-06-17
dc.identifier.urihttp://hdl.handle.net/10713/16076
dc.description.abstractThe SARS-CoV-2 Spike glycoprotein (S protein) acquired a unique new 4 amino acid-PRRA-insertion sequence at amino acid residues (aa) 681–684 that forms a new furin cleavage site in S protein as well as several new glycosylation sites. We studied various statistical properties of the-PRRA-insertion at the RNA level (CCUCGGCGGGCA). The nucleotide composition and codon usage of this sequence are different from the rest of the SARS-CoV-2 genome. One of such features is two tandem CGG codons, although the CGG codon is the rarest codon in the SARS-CoV-2 genome. This suggests that the insertion sequence could cause ribosome pausing as the result of these rare codons. Due to population variants, the Nextstrain divergence measure of the CCU codon is extremely large. We cannot exclude that this divergence might affect host immune responses/effectiveness of SARS-CoV-2 vaccines, possibilities awaiting further investigation. Our experimental studies show that the expression level of original RNA sequence “wildtype” spike protein is much lower than for codon-optimized spike protein in all studied cell lines. Interestingly, the original spike sequence produces a higher titer of pseudoviral particles and a higher level of infection. Further mutagenesis experiments suggest that this dual-effect insert, comprised of a combination of overlapping translation pausing and furin sites, has allowed SARS-CoV-2 to infect its new host (human) more readily. This underlines the importance of ribosome pausing to allow efficient regulation of protein expression and also of cotranslational subdomain folding. © 2021 by the authors.en_US
dc.description.sponsorshipNational Eye Instituteen_US
dc.description.urihttps://doi.org/10.3390/ijms22126490en_US
dc.language.isoenen_US
dc.publisherMDPI AGen_US
dc.relation.ispartofInternational Journal of Molecular Sciencesen_US
dc.subjectCodon usageen_US
dc.subjectRibosome pausing siteen_US
dc.subjectRibosome stallingen_US
dc.subjectSARS-CoV-2en_US
dc.subjectSpike proteinen_US
dc.titleThe functional consequences of the novel ribosomal pausing site in sars-cov-2 spike glycoprotein rnaen_US
dc.typeArticleen_US
dc.identifier.doi10.3390/ijms22126490
dc.source.volume22
dc.source.issue12


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