Linking the function of cis-acting RNA elements to coronavirus replication using interactomes.

RNA structures that are functionally important are defined as cis-acting RNA elements because their functions cannot be compensated for in trans. The cis-acting RNA elements in the 3' UTR of coronaviruses are important for replication; however, the mechanism linking the cis-acting RNA elements to their replication function remains to be established. In the present study, a comparison of the biological processes of the interactome and the replication efficiency between the 3' UTR cis-acting RNA elements in coronaviruses, including severe acute respiratory syndrome coronavirus 2, suggests that (i) the biological processes, including translation, protein folding and protein stabilization, derived from the analysis of the cis-acting RNA element interactome and (ii) the architecture of the cis-acting RNA elements and their interactomes are highly correlated with coronavirus replication. In addition, alteration of the interactome using the compound 5-benzyloxygramine can cause reduced coronavirus replication, reinforcing the connection between cis-acting RNA elements and replication by interactome. Together, these results link cis-acting RNA elements to the coronavirus replication and establish a model to analyse the cis-acting RNA elements in the replication of RNA viruses by interactome.