PRMT7, a New Protein Arginine Methyltransferase That Synthesizes Symmetric Dimethylarginine

Abstract

The cDNA for PRMT7, a recently discovered human protein-arginine methyltransferase (PRMT), was cloned and expressed in Escherichia coli and mammalian cells. Immunopurified PRMT7 actively methylated histones, myelin basic protein, a fragment of human fibrillarin (GAR) and spliceosomal protein SmB. Amino acid analysis showed that the modifications produced were predominantly monomethylarginine and symmetric dimethylarginine (SDMA). Examination of PRMT7 expressed in E. coli demonstrated that peptides corresponding to sequences contained in histone H4, myelin basic protein, and SmD3 were methylated. Furthermore, analysis of the methylated proteins showed that symmetric dimethylarginine and relatively small amounts of monomethylarginine and asymmetric dimethylarginine were produced. SDMA was also formed when a GRG tripeptide was methylated by PRMT7, indicating that a GRG motif is by itself sufficient for symmetric dimethylation to occur. Symmetric dimethylation is reduced dramatically compared with monomethylation as the concentration of the substrate is increased. The data demonstrate that PRMT7 (like PRMT5) is a Type II methyltransferase capable of producing SDMA modifications in proteins.

Mammalian Protein Arginine Methyltransferase 7 (PRMT7) Specifically Targets RXR Sites in Lysine- and Arginine-rich Regions

“…Previous results suggesting that PRMT7 has the ability to form ADMA and/or SDMA (9,16,20) may have been compromised by contamination of enzyme preparations with other PRMTs, particularly when FLAG-tagged PRMT7 is purified in a protocol also known to purify nontagged PRMT5 (2,3,5,19). Endogenous PRMT5 in mammalian cells has an affinity for the monoclonal M2 antibody used to purify FLAG-tagged proteins (19).…”

“…A sole type III activity forming MMA has been reported (4,5) as well as a type I/type II activity forming both ADMA and SDMA (16). A sole type III activity was also found for the worm and trypanosome homologs of PRMT7 (17,18).…”

A Mendelian locus on chromosome 16 determines susceptibility to doxorubicin nephropathy in the mouse

“…Methylation of doxorubicin has also been reported to decrease its cytotoxic potential (30), raising the possibility that direct methylation of doxorubicin by Prmt7 may mediate protection from kidney injury. The biological role and the natural substrate(s) for Prmt7 are yet unknown, but available data suggest that it is a type II methyltransferase (31,32). Prmt7 has conserved orthologs in many species, including Drosophila menalogaster and Caenorhabditis elegans, and was recently identified in a screen of genes conferring sensitivity to many DNA damaging agents, suggesting a role in cellular response to xenobiotics (20).…”

Molecular characterisation and inductive expression of a fish protein arginine methyltransferase 1 gene in response to virus infection

“…Based on their reaction product specificity, these enzymes are divided into two major classes: type I PRMTs promote the formation of u-monomethylarginine and asymmetric u-N G ,N G -dimethylarginine (aDMA), and type II PRMTs catalyse the formation of u-monomethylarginine and symmetric u-N G ,N G -dimethylarginine (sDMA) [1]. In mammals, six type I PRMT enzymes, such as PRMT1 [2], PRMT2 [3], PRMT3 [4], CARM1 (PRMT4) [5], PRMT6 [6] and PRMT8, have been identified, and type II enzymes identified to date include the Janus kinase-binding protein JBP1/PRMT5 [7], and PRMT7 [8,9]. The recently identified FBXO11/PRMT9 should belong to type II PRMT family although it contains a unique N-terminal F-box domain that does not appear in the other known PRMT enzymes [10].…”