2'-O-Methyl-5-hydroxymethylcytidine: A Second Oxidative Derivative of 5-Methylcytidine in RNA

J Am Chem Soc. 2017 Feb 8;139(5):1766-1769. doi: 10.1021/jacs.6b12180. Epub 2017 Jan 25.


5-Hydroxymethylcytidine (hm5C) was recently identified as a direct metabolite of m5C in RNA. We investigated the stability of hm5C in human cells using bio-isotopologues and LC-MS/HRMS. This has led to the discovery of a second oxidative metabolite of m5C in RNA, namely 2'-O-methyl-5-hydroxymethylcytidine (hm5Cm). Subsequent quantitative analysis of total RNA from higher organisms revealed varying levels and TET-independent formation of this new RNA modification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • Chromatography, Liquid
  • Cytidine / analogs & derivatives*
  • Cytidine / chemistry
  • Cytidine / metabolism
  • HEK293 Cells
  • Humans
  • Mice
  • Molecular Structure
  • Oxidation-Reduction
  • RNA / chemistry*
  • RNA / metabolism
  • Tandem Mass Spectrometry


  • 2'-O-methyl-5-hydroxymethylcytidine
  • Cytidine
  • RNA
  • 5-methylcytidine