Protein Arginine Methylation in Mammals: Who, What, and Why

Abstract

The covalent marking of proteins by methyl group addition to arginine residues can promote their recognition by binding partners or can modulate their biological activity. A small family of gene products that catalyze such methylation reactions in eukaryotes (PRMTs) work in conjunction with a changing cast of associated subunits to recognize distinct cellular substrates. These reactions display many of the attributes of reversible covalent modifications such as protein phosphorylation or protein lysine methylation; however, it is unclear to what extent protein arginine demethylation occurs. Physiological roles for protein arginine methylation have been established in signal transduction, mRNA splicing, transcriptional control, DNA repair, and protein translocation.

Methylation by protein arginine methyltransferase 1 increases stability of Axin, a negative regulator of Wnt signaling

“…As shown in Figure 2a, only wild-type (WT) GST-PRMT1 methylated the N-terminus of Axin, compared with dominantnegative GST-PRMT1 which has no enzymatic activity (McBride et al, 2000). PRMT1 is a type I arginine methyltransferase, a group that includes PRMT3, PRMT4/Carm1 and PRMT6 (Bedford and Clarke, 2009), and has several splicing variants (Goulet et al, 2007). Among them, PRMT1, PRMT3 and PRMT6 methylate substrates have a conserved glycine/argininerich (GAR) motif, whereas PRMT4/Carm1 has different motif (Boisvert et al, 2005).…”

“…Recent studies have suggested that arginine methylation of proteins has critical roles in the regulation of diverse biological processes (Bedford, 2007). Protein arginine methyltransferases (PRMTs) are responsible for this modification and are classified into two groups based on their generation of either asymmetric or symmetric dimethylarginine (Bedford and Clarke, 2009). Protein arginine methyltransferase 1 (PRMT1) is a type-I methyltransferase that transfers a methyl group from S-adenosylmethionine to the guanido nitrogens of arginine residues, forming monomethylarginine and asymmetric dimethylarginine (Bedford and Richard, 2005).…”

Diversity within the pRb pathway: is there a code of conduct?

“…Methylation by methyltransferases can occur on both lysine and arginine residues. A large number of methyltransferases have been identified, which can loosely be divided into two subgroups; lysine methyltransferases, mostly belonging to the SET domain family (Martin and Zhang, 2005), and arginine methyltransferase, referred to as protein arginine dimethyltransferases (Bedford and Clarke, 2009). Very interestingly, pRb is methylated by the mono-methyltransferase Set7/9 at two distinct lysine residues within the C-terminal domain of pRb, K873 and K810 (Munro et al, 2010;Carr et al, 2011) (Figure 1).…”

Histone Arginine Methylation by PRMT7 Controls Germinal Center Formation via Regulating Bcl6 Transcription

“…The physiological functions of histone arginine methylation play roles in numerous processes, such as cell differentiation, embryonic development, and carcinogenesis (14,15). In mammals, nine members of the PRMT family catalyze mono-, asymmetric di-, and symmetric dimethylated arginine residues (16).Unlike the other members, PRMT7 is unique owing to its controversial catalyzed arginine types. Initially, Miranda et al (17) identified PRMT7 as a member of the PRMT family that catalyzed the formation of v-N G -monomethyl-arginine residues on synthetic peptides in vitro, whereas later in the year another team (18) reported that PRMT7 could methylate both peptides and proteins to form symmetric dimethylated arginine residues.…”