Regulation of RNA Methylation by TET Enzymes

The ten-eleven-translocation (TET1/2/3) proteins are capable of oxidizing 5-methylcytosine (m5C) to 5-hydroxymethylcytosine (hm5C) and further oxidized derivatives in the process of active demethylation to cytosine. This process has been investigated almost exclusively in the context of DNA demethylation and epigenetics. However, a handful of recent studies have demonstrated that m5C and TET protein-mediated oxidation are also important in the context of the epitranscriptome and mRNA, leading to modified RNA binding protein profiles and ultimately altering translation efficiency and mRNA stability. Here we summarize the current state of knowledge on the presence and function of m5C in eukaryotic mRNA and its oxidation.