METTL4

N(6)-adenine-specific methyltransferase that can methylate both RNAs and DNA. Acts as a N(6)-adenine-specific RNA methyltransferase by catalyzing formation of N6,2'-O-dimethyladenosine (m6A(m)) on internal positions of U2 small nuclear RNA (snRNA): methylates the 6th position of adenine residues with a pre-deposited 2'-O-methylation. Internal m6A(m) methylation of snRNAs regulates RNA splicing. Also able to act as a N(6)-adenine-specific DNA methyltransferase by mediating methylation of DNA on the 6th position of adenine (N(6)-methyladenosine). The existence of N(6)-methyladenosine (m6A) on DNA is however unclear in mammals, and additional evidence is required to confirm the role of the N(6)-adenine-specific DNA methyltransferase activity of METTL4 in vivo. Acts as a regulator of mitochondrial transcript levels and mitochondrial DNA (mtDNA) copy number by mediating mtDNA N(6)-methylation: m6A on mtDNA reduces transcription by repressing TFAM DNA-binding and bending. N(6)-methyladenosine deposition by METTL4 regulates Polycomb silencing by triggering ubiquitination and degradation of sensor proteins ASXL1 and MPND, leading to inactivation of the PR-DUB complex and subsequent preservation of Polycomb silencing (By similarity)..

Function from UniProtKB (Q8N3J2), read 2026-09-23. CC BY 4.0.