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.

Keywords

Animals, Brain, Chromatography, Liquid, Cytidine, HEK293 Cells, Humans, Mice, Molecular Structure, Oxidation-Reduction, RNA, Tandem Mass Spectrometry

Journal Title

Journal of the American Chemical Society

Journal ISSN

0002-7863
1520-5126

Volume Title

139

Publisher

American Chemical Society

Publisher DOI

https://doi.org/10.1021/jacs.6b12180

Rights and licensing

Except where otherwised noted, this item's license is described as http://www.rioxx.net/licenses/all-rights-reserved

Sponsorship

Wellcome Trust (099232/Z/12/Z)

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).

Collections

Scholarly Works - Chemistry
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