THE PREDOMINANT PROTEIN-ARGININE METHYLTRANSFERASE FROM SACCHAROMYCES-CEREVISIAE

We have identified the major enzymatic activity responsible for the S- adenosyl-L-methionine-dependent methylation of arginine residues (EC 2 .1.1.23) in proteins of the yeast Saccharomyces cerevisiae. The RMT1 ( protein-arginine methyltransferase), formerly ODP1, gene product encod es a 348-residue polypeptide of 39.8 kDa that catalyzes both the N-G-m ono- and N-G,N-G-asymmetric dimethylation of arginine residues in a va riety of endogenous yeast polypeptides. A yeast strain in which the ch romosomal RMT1 gene was disrupted is viable, but the level of N-G,N-G- [H-3]dimethylarginine residues detected in intact cells incubated with S-adenosyl-L-[methyl-H-3]methionine is reduced to less than 15% of th e levels found in the parent strain, while the N-G-[H-3]monomethylargi nine content is reduced to less than 30%. We show that soluble extract from parent cells, but not from mutant rmt1 cells, catalyzes the in v itro methylation of endogenous polypeptides of 55, 41, 38, 34, and 30 kDa. The hypomethylated form of these five polypeptides, as well as th at of several others, can be mono- and asymmetrically dimethylated by incubating the mutant rmt1 extract with a purified, bacterially produc ed, glutathione S-transferase-RMT1 fusion protein and S-adenosyl-L-[me thyl-H-3]methionine. This glutathione S-transferase-RMT1 fusion protei n is also able to methylate a number of mammalian polypeptides includi ng histones, recombinant heterogeneous ribonucleoprotein A1, cytochrom e c, and myoglobin, but cannot methylate myelin basic protein. RMT1 ap pears to be a yeast homolog of a recently characterized mammalian prot ein-arginine methyltransferase whose activity may be modulated by mito tic stimulation of cells.