Biochemistry and regulation of the protein arginine methyltransferases (PRMTs)

• Protein arginine methyltransferases (PRMTs) methylate protein arginyl groups.
• PRMT substrates of nine mammalian isoforms show no consensus sequence.
• PRMTs can form monomethyl-, asymmetric dimethyl- or symmetric dimethylarginine.
• Biological function is dependent upon specific product formation.
• Processivity, regulators and posttranslational modifications control activity.

Many key cellular processes can be regulated by the seemingly simple addition of one, or two, methyl groups to arginine residues by the nine known mammalian protein arginine methyltransferases (PRMTs). The impact that arginine methylation has on cellular well-being is highlighted by the ever growing evidence linking PRMT dysregulation to disease states, which has marked the PRMTs as prominent pharmacological targets. This review is meant to orient the reader with respect to the structural features of the PRMTs that account for catalytic activity, as well as provide a framework for understanding how these enzymes are regulated. An overview of what we understand about substrate recognition and binding is provided. Control of product specificity and enzyme processivity are introduced as necessary but flexible features of the PRMTs. Precise control of PRMT activity is a critical component to eukaryotic cell health, especially given that an arginine demethylase has not been identified. We therefore conclude the review with a comprehensive discussion of how protein arginine methylation is regulated.