Chemistry and biology of oxidatively damaged RNA nucleotides

Abstract

Nucleic acid damage under oxidative stress conditions is a well-established phenomenon relevant to evolution of all living organisms. While well investigated for DNA, cellular RNAs are also a subject of extensive damage, featuring similar reactivity towards reactive oxygen species generated by external factors and cellular metabolism. The chemistry of DNA and RNA oxidative damage is rather complex, involving a variety of concomitant chemical reactions which are further exacerbated by secondary reactions that increase the already overwhelming list of chemically damaged nucleotides. The damage is of random character, typically resulting in sub-stoichiometrically damaged sites. This substantially complicates the analysis of RNA oxidation. Modern analytical techniques include deep sequencing-based protocols allowing precise mapping of such damaged residues in cellular RNAs. Increasing experimental evidence suggests vast and widespread biological consequences and highlights the importance of the metabolism of oxidized RNA in a variety of cellular processes. The main effects are expected at the level of translation, since all key players of the translational machinery, mRNA, rRNA and tRNAs are prominent oxidation targets. In this review we present current achievements in the analysis of RNA oxidation/damage chemistry, traditional and modern methods allowing RNA oxidation analysis and current view on the biological consequences of RNA oxidation in the living cell.