Roles and Dynamics of 3-methylcytidine in Cellular RNAs

Modified nucleotides within cellular RNAs significantly influence their biogenesis, stability, and function. As reviewed here, 3-methylcytidine (mC) has recently come to the fore through the identification of the methyltransferases responsible for installing mC in human tRNAs. Mechanistic details of how mC methyltransferases recognize their substrate tRNAs have been uncovered and the biogenetic and functional relevance of interconnections between mC and modified adenosines at position 37 highlighted. Functional insights into the role of mC modifications indicate that they influence tRNA structure and, consistently, lack of mC modifications impairs translation. Development of quantitative, transcriptome-wide mC mapping approaches and the discovery of an mC demethylase reveal mC to be dynamic, raising the possibility that it contributes to fine-tuning gene expression in different conditions.