Shared properties and singularities of exoribonuclease-resistant RNAs in viruses

What viral RNA genomes lack in size, they make up for in intricacy. Elaborate RNA structures embedded in viral genomes can hijack essential cellular mechanisms aiding virus propagation. Exoribonuclease-resistant RNAs (xrRNAs) are an emerging class of viral elements, which resist degradation by host cellular exoribonucleases to produce viral RNAs with diverse roles during infection. Detailed three-dimensional structural studies of xrRNAs from flaviviruses and a subset of plant viruses led to a mechanistic model in which xrRNAs block enzymatic digestion using a ring-like structure that encircles the 5′ end of the resistant structure. In this mini-review, we describe the state of our understanding of the phylogenetic distribution of xrRNAs, their structures, and their conformational dynamics. Because xrRNAs have now been found in several major superfamilies of RNA viruses, they may represent a more widely used strategy than currently appreciated. Could xrRNAs represent a ‘molecular clock’ that would help us understand virus evolution and pathogenicity? The more we study xrRNAs in viruses, the closer we get to finding xrRNAs within cellular RNAs.