Methyltransferases

Methyltransferases are enzymes that catalyze the transfer of a methyl group from a donor, most commonly S-adenosyl-L-methionine (SAM), to acceptor substrates such as nucleic acids, proteins, or small molecules. The reaction typically converts SAM to S-adenosyl-L-homocysteine (SAH). Methylation patterns defined by these enzymes influence gene expression, RNA processing, protein function, and metabolic regulation.

Methyltransferases are classified by their substrates. DNA methyltransferases (DNMTs) methylate cytosine residues in DNA, contributing to gene regulation, imprinting, and developmental processes. RNA methyltransferases modify RNA, with examples including the METTL3/METTL14 complex that installs N6-methyladenosine (m6A) in mRNA, along with enzymes acting on tRNA and rRNA. Protein methyltransferases (PMTs) modify amino acid side chains, most commonly lysine or arginine residues on histones and other proteins. Histone methyltransferases (HMTs) establish chromatin states that influence transcription; examples include SET-domain enzymes and the arginine methyltransferases (PRMTs). Other PMTs modify non-histone proteins, affecting signaling and enzyme activity. In bacteria, methyltransferases participate in restriction-modification systems and gene expression regulation.

Mechanistically, many methyltransferases are SAM-dependent and share structural features for binding SAM and the substrate, transferring the methyl group in a nucleophilic attack that yields SAH and the methylated product. Reversibility occurs through demethylation pathways for DNA and histone marks, enabling dynamic regulation.

Biological importance and clinical relevance accompany their diversity. Aberrant DNA methylation patterns are linked to cancer and neurological disorders, while histone and RNA methylation influence development and cellular responses. Inhibitors targeting DNMTs or certain histone methyltransferases are used or explored in therapeutic contexts.