The impact of non-synonymous mutations on miRNA binding sites within the SARS-CoV-2 NSP3 and NSP4 genes

Autor: S. M. Ali Hosseini Rad, Dhammika Leshan Wannigama, Nattiya Hirankarn, Alexander D. McLellan
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Scientific Reports, Vol 13, Iss 1, Pp 1-6 (2023)
Druh dokumentu: article
ISSN: 2045-2322
62668544
DOI: 10.1038/s41598-023-44219-y
Popis: Abstract Non-synonymous mutations in the SARS-CoV-2 spike region affect cell entry, tropism, and immune evasion, while frequent synonymous mutations may modify viral fitness. Host microRNAs, a type of non-coding RNA, play a crucial role in the viral life cycle, influencing viral replication and the host immune response directly or indirectly. Recently, we identified ten miRNAs with a high complementary capacity to target various regions of the SARS-CoV-2 genome. We filtered our candidate miRNAs to those only expressed with documented expression in SARS-CoV-2 target cells, with an additional focus on miRNAs that have been reported in other viral infections. We determined if mutations in the first SARS-CoV-2 variants of concern affected these miRNA binding sites. Out of ten miRNA binding sites, five were negatively impacted by mutations, with three recurrent synonymous mutations present in multiple SARS-CoV-2 lineages with high-frequency NSP3: C3037U and NSP4: G9802U/C9803U. These mutations were predicted to negatively affect the binding ability of miR-197-5p and miR-18b-5p, respectively. In these preliminary findings, using a dual-reporter assay system, we confirmed the ability of these miRNAs in binding to the predicted NSP3 and NSP4 regions and the loss/reduced miRNA bindings due to the recurrent mutations.
Databáze: Directory of Open Access Journals
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