2'-$\textit{0}$-Methyl-5-hydroxymethylcytidine: A Second Oxidative Derivative of 5-Methylcytidine in RNA

5-Hydroxymethylcytidine (hm$^{5}$C) was recently identified as a direct metabolite of m$^{5}$C in RNA. We investigated the stability of hm$^{5}$C in human cells using bio-isotopologues and LC-MS/HRMS. This has led to the discovery of a second oxidative metabolite of m$^{5}$C in RNA, namely 2′-$\textit{0}$-methyl-5-hydroxymethylcytidine (hm$^{5}$C$\textit{m}$). Subsequent quantitative analysis of total RNA from higher organisms revealed varying levels and TET-independent formation of this new RNA modification.This work was supported by a Wellcome Trust Senior Investigator award to SB (grant no. 099232/z/12/z). The Balasubramanian group is supported by core funding from Cancer Research U.K. (C14303/A17197)