Ribonucleobase Oxidation and Ribonucleases Involved in the Degradation of Oxidized RNA

Oxidation of RNA has gained interest from the community due, in part, to a link in the progression/development of disease as well as other biological processes such as apoptosis, ageing, hibernation, and signalling, amongst others. Different types of RNA with varying functions and size have been shown to be oxidized in vivo, including ribosomal RNA (rRNA), transfer RNA (tRNA), microRNA (miRNA), messenger RNA (mRNA), and mitochondrial RNA (mtRNA). This process occurs from reactions between reactive oxygen species (ROS) and all biopolymers, including RNA, from endogenous as well as exogenous sources. As a consequence, mechanisms that handle oxidized RNA are important, and enzymatic degradation is the most commonly studied process to date. This review focuses on the ribonucleases that have been shown to play a role in the degradation of oxidized RNA. While emphasis is placed on, arguably, the most common oxidatively generated chemical modification, 8-oxo-7,8-dihydroguanosine (8-oxoG), the products that arise from the oxidation of other canonical nucleosides as well as naturally occurring modifications are also discussed in the context of RNA oxidation. Processing of oxidized RNA via its enzymatic degradation is likely the main route, but a potential role of other proteins involved in the handling of oxidized RNA is hypothesized, e.g., helicases, export proteins, and extracellular environments. We postulate that this is an area with great potential for discovery.