The major focus of my laboratory is elucidating the biological role of arginine methylation. Arginine methylation is a very common posttranslational modification, that occurs predominantly in the nucleus. The main pool of proteins modified in this way possess RNA binding properties. In addition, enzymes that facilitate histone acetylation (CBP/p300) and histones themselves are also arginine methylated - thus implicating this modification in transcriptional regulation. The methylation of arginine residues is catalyzed by at least two different classes of protein arginine methyltransferase (PRMT) enzymes. The Type I enzymes catalyze the formation of asymmetric NG,NG-dimethylarginine (aDMA) residues and the Type II enzymes catalyze the formation of symmetric NG,N'G-dimethylarginine (sDMA) residues. Both enzyme types generate NG-monomethylarginine (MMA) intermediates. In mammals, four Type I enzymes (PRMT1, 3, 4, 6 & 8) and a single Type II enzyme (PRMT5) have been described. The activity of PRMT2, PRMT7 and PRMT9 has not yet been determined. Regions of proteins that are methylated are often, but not always, glycine and arginine-rich and are referred to as GAR motifs. The direct biological consequences of arginine methylation are at the level of protein-protein interactions. More broadly, arginine methylation has been implicated in a variety of cellular processes, including protein trafficking, signal transduction and transcriptional regulation. In my laboratory, we are taking a three-pronged approach to further explore the biological roles of protein arginine methylation.