Structures and mechanisms of the RNA m6A writer

• The m6A writer complex comprises a catalytic core (METTL3/METTL14) and a regulatory module (HAKAI, WTAP, VIRMA, ZC3H13, RBM15/15B) that together ensure substrate specificity and efficient methylation. • Structural studies have revealed how METTL3/METTL14 heterodimer recognizes RNA substrates and positions the methyl donor SAM for targeted m6A deposition. • The review highlights the molecular mechanisms underlying selective m6A modification, which is critical for understanding gene expression regulation and disease pathogenesis. • Advances in structural biology provide a framework for developing therapeutic interventions targeting m6A writers in cancers and other diseases.