RNA genome conservation and secondary structure in SARS-CoV-2 and SARS-related viruses

Ramya Rangan; Ivan N. Zheludev; Rhiju Das

The RNAz approach led to the prediction of 44 structured genome loci comprising 117 windows with predicted structure (P>0.9), with these loci covering 46% of the SARS-CoV-2 genome ( Figure 3 ). We found that five canonical RNA structures (the frameshifting element, the 3´ UTR pseudoknot, the 3´ UTR hypervariable region, 5´ UTR SL2-3, and 5´ UTR SL5) were present in these loci. Additionally, conserved SARS-CoV-2 regions overlap significantly with predicted RNAz loci, with 62 of 78 SARS-CoV-2 conserved intervals at a 97% sequence cutoff overlapping by at least 15 nucleotides with RNAz loci. This enrichment is statistically significant (p-value<0.001 from comparisons to 10,000 random placements of conserved intervals). This enrichment also holds when considering overlaps with conserved regions from SARSr-MSA-1; 124 of the 229 SARSr-MSA-1 conserved intervals at a 90% conservation cutoff overlap by at least 15 nucleotides with RNAz loci (p-value 0.0038). This analysis potentially expands the set of conserved structural regions of SARS-CoV-2 beyond known Rfam families and those noted in the literature (full set of RNAz loci in Supplementary File 1). Topscoring structured windows from RNAz that overlap with conserved sequence regions in SARS-CoV-2-MSA-2 for at least 15 nucleotides are included in Table 2 ; we termed these SARS-CoV-2conserved-structured regions. Overlapping intervals between the RNAz predictions and conserved sequence regions in SARSr-MSA-1 are included in Supplementary File 1.