Abstract:Over 100 types of chemical modifications have been identified in various types of RNAs including rRNA, tRNA, snRNA, snoRNA and mRNA, among which methylation is most common. The N6-methyl-adenosine (m6A) as the most common and abundant internal modification on mRNA molecules has been widely studied. The recent identification of m6A modifying enzymes including methyltransferase complex METTL3/METTL14/WTAP, two demethylases ALKBH5 and FTO and binding proteins YTHDF2, YTHDF1 and YTHDC1, indicates that RNA methylation is reversible and represents a novel epitranscriptomic mechanism instead of micro-regulation in gene expression control. Identification of candidate m5C modifying enzymes NSUN family proteins and TET proteins further expands RNA methylation-mediated epitranscriptomics. Epitranscriptomics has become a new research frontier in RNA biology. This review summarizes recent progress in RNA m6A and m5C methylations and proposes their potential biological significance.