Figure 1. The m6A methylation machinery and the biological functions of m6A.
The m6A modification is installed onto mRNA by the methyltransferase complex (Writers) comprising of the METTL3-METTL14 heterodimer core subunit and other cofactors, including WTAP, KIAA1429, ZC3H13, and RBM15/RBM15b. METTL16 alone can catalyze m6A formation in U6 snRNA and some structured RNAs, while ZCCHC4 is responsible for deposition of m6A on rRNA. The RNA m6A modification can be reversibly removed by RNA demethylases (Erasers) FTO and ALKBH5. The biological functions of m6A modification are achieved by specific recognition and binding by RNA binding proteins (Readers), which affects RNA fate by regulating RNA splicing, export, decay, stabilization, and translation.
