RNA self-cleavage activated by ultraviolet light-induced oxidation

Abstract

A novel UV-C-light-induced ribozyme activity was discovered within the highly structured 5′-genomic regions of both Hepatitis C Virus (HCV) and the related Classic Swine Fever Virus (CSFV). Cleavage is mediated by exposure to UV-C light but not by exogenous oxygen radicals. It is also very selective, occurring at base positions HCV C 79 and CSFV A 45 in some molecules and at the immediately adjacent 5′-positions HCV U 78 and CSFV U 44 in others. Among other reaction products, the majority of biochemically active products detected contained 3′-phosphate and 5′-phosphate-end groups at the newly generated termini, along with a much lower amount of 3′-hydroxyl end group. While preservation of an E-loop RNA structure in the vicinity of the cleavage site was a requisite for HCV RNA self-cleavage, this was not the case for CSFV RNA. The short size of the reactive domains (∼33 nt), which are compatible with primitive RNA motifs, and the lack of sequence homology, indicate that as-yet unidentified UV-activated ribozymes are likely to be found throughout structured RNAs, thereby providing clues to whether early RNA self-cleavage events were mediated by photosensitive RNA structures.