A conserved long-range RNA interaction in SARS-CoV-2 recruits ADAR1 to enhance virus proliferation [dataset2]

Various SARS-CoV-2 viruses have caused the COVID-19 pandemic world-wide. As the viruses evolve different mutations along their genomes, these mutations can impact virus RNA structures and their phenotypes. Here we probe the RNA structures across Wuhan, alpha, beta, delta and omnicron strains of the SARS-CoV-2 viruses. We observe that while the mutations impact RNA structures, it is not the main source of RNA structure changes (RBPs?). Structurally conserved structures are enriched for both long and short RNA pair-wise interactions. We identified a conserved 17kb long range interaction that decreases the virus fitness when mutated. Additionally, this interaction binds to ADAR1 to alter editing levels on the virus. These studies reveal the importance of RNA structures along virus genomes to facilitate virus infectivity. Overall design: A-to-I editing of WT SARS-CoV-2 in E6 TMPRSS2 Vero cells