PRMT-5 converts monomethylarginines into symmetrical dimethylarginines in Caenorhabditis elegans.
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.
Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8577, Japan.
Akihiko
A
Kanou
Faculty of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8577, Japan.
Koichiro
K
Kako
Faculty of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8577, Japan.|PhD Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8577, Japan.
Keiko
K
Hirota
Life Science Center of Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8577, Japan.
Akiyoshi
A
Fukamizu
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D002853:Chromatography, Liquid; D008745:Methylation; D009154:Mutation; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
D029742:Caenorhabditis elegans Proteins; C487735:dimethylarginine; D001120:Arginine; D011484:Protein-Arginine N-Methyltransferases; C584313:prmt-5 protein, C elegans
Caenorhabditis elegans; arginine methylation; protein arginine methyltransferase; acid hydrolysis; LC-MS/MS