Methyltransfer

Methyltransfer, or methyltransferase (MTase), is an enzyme that catalyzes the transfer of a methyl group from a donor to an acceptor substrate. The most common methyl donor is S-adenosyl-L-methionine (SAM). In a typical reaction, SAM donates a methyl group and is converted to S-adenosylhomocysteine (SAH), while the substrate becomes methylated. MTases are widespread across all domains of life and participate in a variety of cellular processes.

Based on substrate they act on, methyltransferases are grouped into DNA methyltransferases, RNA methyltransferases, protein methyltransferases, and small-molecule methyltransferases. DNA MTases modify cytosine or adenine bases and are central to epigenetic regulation, imprinting, and genome defense. RNA MTases modify rRNA, tRNA, and mRNA, influencing RNA stability, splicing, translation. Protein MTases methylate lysine, arginine, or other residues, regulating enzyme activity, protein-protein interactions, and chromatin structure. Small-molecule MTases methylate neurotransmitter substrates, hormones, and metabolites, often participating in detoxification and biosynthesis.

Most MTases are SAM-dependent; the activity is linked to cellular SAM/SAH levels, and SAH acts as a feedback inhibitor. Some MTases use alternative donors or cofactors, and a few non-SAM-dependent methyltransferase activities exist. Structurally, many MTases share a conserved Rossmann-like fold and characteristic SAM-binding motifs, though the overall architecture varies with substrate class.

Because methylation alters chemical properties and interactions, MTases influence gene expression, RNA processing, protein function, and metabolite production. In humans, dysregulation of DNA and histone methyltransferases is associated with cancer and developmental disorders. MTases are targets for drugs, and their activities are exploited in research and biotechnology, such as mapping methylomes, synthetic biology, and the production of methylated compounds.