Self-cleaving ribozymes conserved in RNA viruses unveil a new role in protein translation

Abstract

AbstractSmall self-cleaving ribozymes are catalytic RNAs originally discovered in viroid-like agents, which are infectious circular RNAs (circRNAs) postulated as relics of a prebiotic RNA world. In the last decade, however, small ribozymes have also been detected across the tree of life, from bacterial to human genomes, and more recently, in viral agents with circRNA genomes. Here we report the conserved occurrence of small ribozymes within the linear genomes of typical ds and ssRNA viruses from fungi and plants. In most 5’-UTR regions of chrysovirids and fusarivirids, we find conserved type I hammerhead ribozymes (hhrbzs) showing efficient self-cleaving activityin vitroandin vivo. Similar hhrbzs, as well as hepatitis delta and twister ribozymes, were also detected in megabirna-, hypo-, fusagra- and toti-like viruses. These ribozymes occur as isolated motifs but also as close tandem pairs, suggesting that they are involved in the formation of ∼300 nt circRNAs.In vivocharacterization of a chrysovirid hhrbz revealed its unexpected role in protein translation as an internal ribosome entry site (IRES). RNA structural comparison between the hammerhead three-way junction and the core domain of picornavirus IRES elements allow us to suggest that these simple ribozymes may follow a similar strategy to achieve cap-independent translation. We conclude that self-cleaving ribozymes, historically involved in the rolling circle replication of viroid-like agents, have been exapted towards translational functions in linear RNA viruses.