PRMT-5 converts monomethylarginines into symmetrical dimethylarginines in Caenorhabditis elegans

• Published in: Journal of biochemistry (Tokyo) Vol. 161; no. 2; pp. 231 - 235
• Main Authors: Kanou, Akihiko, Kako, Koichiro, Hirota, Keiko, Fukamizu, Akiyoshi
• Format: Journal Article
• Language: English
• Published: England 01.02.2017
• Subjects: Animals; Arginine - analogs & derivatives; Arginine - analysis; Arginine - metabolism; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - isolation & purification; Caenorhabditis elegans Proteins - metabolism; Chromatography, Liquid; Methylation; Mutation; Protein-Arginine N-Methyltransferases - genetics; Protein-Arginine N-Methyltransferases - isolation & purification; Protein-Arginine N-Methyltransferases - metabolism; Tandem Mass Spectrometry; Caenorhabditis elegans; LC-MS/MS; arginine methylation; acid hydrolysis; protein arginine methyltransferase
• ISSN: 0021-924X; 1756-2651
• DOI: 10.1093/jb/mvw066

The transmethylation to arginine residues of proteins is catalyzed by protein arginine methyltransferases (PRMTs) that form monomethylarginine (MMA), asymmetric (ADMA) and symmetric dimethylarginines (SDMA). Although we previously demonstrated that the generation of ADMA residues in whole proteins is driven by PRMT-1 in Caenorhabditis elegans, much less is known about MMA and SDMA in vivo. In this study, we measured the amounts of different methylarginines in whole protein extracts made from wild-type (N2) C. elegans and from prmt-1 and prmt-5 null mutants using liquid chromatography-tandem mass spectrometry. Interestingly, we found that the amounts of MMA and SDMA are about fourfold higher than those of ADMA in N2 protein lysates using acid hydrolysis. We were unable to detect SDMA residues in the prmt-5 null mutant. In comparison with N2, an increase in SDMA and decrease in MMA were observed in prmt-1 mutant worms with no ADMA, but ADMA and MMA levels were unchanged in prmt-5 mutant worms. These results suggest that PRMT-1 contributes, at least in part, to MMA production, but that PRMT-5 catalyzes the symmetric dimethylation of substrates containing MMA residues in vivo.