PRMT1 is the predominant type I protein arginine methyltransferase in mammalian cells

Type I protein arginine methyltransferases catalyze the formation of asymme tric omega-N-G,N-G-dimethylarginine residues by transferring methyl groups from S-adeno syl-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 i dentified as an additional activity of 10-formyltetrahydrofolate dehydrogen ase (FDH) protein. However, immunodepletion of FDH activity in RAT1 cells a nd in murine tissue extracts with antibody to FDH does not diminish type I methyltransferase activity toward the methyl-accepting substrates glutathio ne S-transferase fibrillarin glycine arginine domain fusion protein or hete rogeneous nuclear ribonucleoprotein Al. Similarly, immunodepletion with ant i-FDH antibody does not remove the endogenous methylating activity for hypo methylated proteins present in extracts from adenosine dialdehyde-treated R AT1 cells. In contrast, anti-PRMT1 antibody can remove PRMT1 activity from RAT1 extracts, murine tissue extracts, and purified rat liver FDH preparati ons. Tissue extracts from FDH(+/+), FDH(+/-), and FDH(-/-) mice have simila r protein arginine methyltransferase activities but high, intermediate, and undetectable FDH activities, respectively. Recombinant glutathione S-trans ferase-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.