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. Author manuscript; available in PMC: 2023 Aug 22.
Published in final edited form as: Annu Rev Biochem. 2023 Apr 17;92:145–173. doi: 10.1146/annurev-biochem-052521-035330

Figure 1. Regulation and function of m6A writer proteins.

Figure 1.

a) m6A is deposited co-transcriptionally by a methyltransferase complex which includes METTL3 as the catalytic subunit and additional proteins METTL14, WTAP, RBM15/15B, VIRMA, HAKAI, and ZC3H13. This complex is recruited to RNAs through interactions with H3K36me3 histone marks, transcription factors, and RNA polymerase II (RNA pol II), and its activity can be influenced by transcription rate. METTL3 deposits m6A within the DRACH consensus sequence, which is where the majority of m6A sites within mRNAs reside. b) In the cytoplasm, METTL3 and METTL16 interact with the translation initiation machinery to promote mRNA translation independently of their methyltransferase activity. c) A subset of mRNAs can be methylated by METTL16, which requires distinct sequence and structural elements. METTL16 also deposits m6A in snRNAs and lncRNAs. At the mRNA 5’ end, PCIF1 deposits m6Am adjacent to the cap.