PRMT1 is the predominant type I protein arginine methyltransferase in mammalian cells.
Type I protein arginine methyltransferases catalyze the formation of asymmetric omega-N(G),N(G)-dimethylarginine residues by transferring methyl groups from S-adenosyl-L-methionine to guanidino groups of arginine residues in a variety of eucaryotic proteins. The predominant type I enzyme activity is found in mammalian cells as a high molecular weight complex (300-400 kDa). In a previous study, this protein arginine methyltransferase activity was identified as an additional activity of 10-formyltetrahydrofolate dehydrogenase (FDH) protein. However, immunodepletion of FDH activity in RAT1 cells and in murine tissue extracts with antibody to FDH does not diminish type I methyltransferase activity toward the methyl-accepting substrates glutathione S-transferase fibrillarin glycine arginine domain fusion protein or heterogeneous nuclear ribonucleoprotein A1. Similarly, immunodepletion with anti-FDH antibody does not remove the endogenous methylating activity for hypomethylated proteins present in extracts from adenosine dialdehyde-treated RAT1 cells. In contrast, anti-PRMT1 antibody can remove PRMT1 activity from RAT1 extracts, murine tissue extracts, and purified rat liver FDH preparations. Tissue extracts from FDH(+/+), FDH(+/-), and FDH(-/-) mice have similar protein arginine methyltransferase activities but high, intermediate, and undetectable FDH activities, respectively. Recombinant glutathione S-transferase-PRMT1, but not purified FDH, can be cross-linked to the methyl-donor substrate S-adenosyl-L-methionine. We conclude that PRMT1 contributes the major type I protein arginine methyltransferase enzyme activity present in mammalian cells and tissues.
Tang
J
J
Molecular Biology Institute, UCLA, Los Angeles, California 90095, USA.
Frankel
A
A
Cook
R J
RJ
Kim
S
S
Paik
W K
WK
Williams
K R
KR
Clarke
S
S
Herschman
H R
HR
D000818:Animals; D001120:Arginine / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D008817:Mice, Mutant Strains; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011496:Protein Methyltransferases / Q000145:classification / Q000302:isolation & purification / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011484:Protein-Arginine N-Methyltransferases / Q000145:classification / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D012436:S-Adenosylmethionine / Q000378:metabolism; D000099295:Formyltetrahydrofolate Dehydrogenase
D001120:Arginine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D011496:Protein Methyltransferases; D011484:Protein-Arginine N-Methyltransferases; D012436:S-Adenosylmethionine; D000099295:Formyltetrahydrofolate Dehydrogenase