Abstract
BackgroundThe world is going through the critical phase of COVID-19 pandemic, caused by human coronavirus, SARS-CoV-2. Worldwide concerted effort to identify viral genomic changes across different sub-types has identified several strong changes in the coding region. However, there have not been many studies focusing on the variations in the 5’ and 3’ untranslated regions and their consequences. Considering the possible importance of these regions in host mediated regulation of viral RNA genome, we wanted to explore the phenomenon.MethodsTo have an idea of the global changes in 5’ and 3’-UTR sequences, we downloaded 8595 complete and high-coverage SARS-CoV-2 genome sequence information from human host in FASTA format from Global Initiative on Sharing All Influenza Data (GISAID) from 15 different geographical regions. Next, we aligned them using Clustal Omega software and investigated the UTR variants. We also looked at the putative host RNA binding protein (RBP) and microRNA binding sites in these regions by ‘RBPmap’ and ‘RNA22 v2’ respectively. Expression status of selected RBPs and microRNAs were checked in lungs tissue.ResultsWe identified 28 unique variants in SARS-CoV-2 UTR region based on a minimum variant percentage cut-off of 0.5. Along with 241C>T change the important 5’-UTR change identified was 187A>G, while 29734G>C, 29742G>A/T and 29774C>T were the most familiar variants of 3’UTR among most of the continents. Furthermore, we found that despite the variations in the UTR regions, binding of host RBP to them remains mostly unaltered, which further influenced the functioning of specific miRNAs.ConclusionOur results, shows for the first time in SARS-Cov-2 infection, a possible cross-talk between host RBPs-miRNAs and viral UTR variants, which ultimately could explain the mechanism of escaping host RNA decay machinery by the virus. The knowledge might be helpful in developing anti-viral compounds in future.
Highlights
Outbreak of novel coronavirus SARS-CoV-2 has been proclaimed as a pandemic by the World Health organization (WHO)
We looked at the putative host RNA binding protein (RBP) and microRNA binding sites in these regions by ‘RBPmap’ and ‘RNA22 v2’ respectively
We identified 28 unique variants in SARS-CoV-2 untranslated region (UTR) region based on a minimum variant percentage cut-off of 0.5
Summary
Outbreak of novel coronavirus SARS-CoV-2 has been proclaimed as a pandemic by the World Health organization (WHO). SARS-CoV-2 is an enveloped, positive-sense, single stranded RNA virus of genus Beta-coronavirus (β-CoVs) with the entire genome size of approximately 30kb. This viral genome is composed of about 14 open reading frames (ORF) which encodes both structural and non-structural proteins having a role in their transmission, survival and pathogenesis [1]. The genomic RNA element of SARS-CoV-2 includes 5’-untranslated region (50-UTR) of 265bp length with a methylated cap and a 3’ polyadenylated UTR of length 229 bp, according to the reference sequence from Wuhan. Considering the possible importance of these regions in host mediated regulation of viral RNA genome, we wanted to explore the phenomenon
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