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

Ramya Rangan; Ivan N. Zheludev; Rhiju Das

Interestingly, in SARSr-MSA-1 and SARSr-MSA-2 we found that conserved stretches overlapped with previously curated Rfam 14 families for Coronaviridae RNA secondary structures: the frameshifting stimulation element (Rfam family RF00507), the 3´ UTR pseudoknot (Rfam family RF00165), and the 3´ stem-loop II-like motif (Rfam family RF00164) (Fig. 2) . Locations for the frameshifting stimulation element, 3´ UTR pseudoknot, and 3´ stem-loop II-like motif were confirmed using Infernal, 15 with all regions discovered at an E<10 -4 threshold. We also found overlap between conserved stretches and additional 5´ UTR structures that have been established for previous coronaviruses, including the original SARS virus, including stem loops 2-3 (SL2-3) and stem loop 5 (SL5). 16 These five known RNA structures overlap with conserved regions more than expected; in 10,000 random trials, the chance that five randomly chosen intervals of these lengths all overlap with the conserved regions from SARSr-MSA-1 or SARSr-MSA-2 is less than 0.0003. The enrichment of known RNA structures in these conserved regions suggests that other conserved regions may also harbor RNA structures.