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Capped mRNAs are methylated by multiple enzymes recruited by the phosphorylated CTD of RNA polymerase II (RNAP). First, RNMT-RAM methylate the cap to create m7G. Second, the 2’-O of the first transcribed nucleotide is methylated by CMTR1. If this nucleotide is an adenosine, it can be further methylated by PCIF1 at the N6 position to create an m6Am modification. The resultant m7Gppp-m6Am modification can suppress translation efficiency and stabilize certain mRNAs.
