N(6)-adenine-specific methyltransferase METTL4 (METTL4)

N(6)-adenine-specific methyltransferase METTL4 (METTL4) is an enzyme of the MT-A70 family that catalyzes N6-methylation of 2’-O-methyladenosine (Am) to form N6,2’-O-dimethyladenosine (m6Am) at internal positions of U2 small nuclear RNA (snRNA), thereby regulating RNA splicing and pre-mRNA processing[1][2][3]. METTL4 recognizes and modifies RNA substrates through a conserved catalytic DPPW motif and utilizes S-adenosylmethionine (SAM) as the methyl group donor. The enzyme is also implicated in the regulation of mitochondrial transcript levels and mitochondrial DNA (mtDNA) copy number, potentially via N6-methyladenosine modification on mtDNA, although the physiological significance and prevalence of DNA methylation activity in mammals remain under debate[3][4]. Recent evidence links METTL4-mediated mtDNA modifications to the progression of diseases such as atherosclerosis; additionally, METTL4 may play broader roles in epigenetic regulation, including repression of Polycomb target genes[3][5]. There are currently no specific inhibitors or drugs targeting METTL4 in clinical use.

Other names

Methyltransferase-like protein 4N(6)-adenine-specific DNA methyltransferase METTL4METTL4_HUMANFLJ23017HsT661snRNA (2'-O-methyladenosine-N(6))-methyltransferase METTL4methyltransferase like 4