A Functional Analysis of Arginine Methylation

PROJECT SUMMARY/ABSTRACT Our goal is to broadly understand the biological roles of arginine methylation, a very common post-translational modification (PTM). This PTM is deposited by at least nine protein arginine methyltransferases (PRMTs) in mammals. Like lysine methylation, arginine methylation of a substrate often recruits an effector molecule to the

newly created methyl-motifs. Unlike lysine methylation, relatively few effects have been identified for methylarginine marks. This paucity of identified methylarginine (Rme) mark effectors and the signaling roles of the known effectors define a knowledge gap that will be addressed here. By performing proteomic screens, we

have identified a novel reader for Rme marks, called SART3. This effector does not harbor a Tudor domain which is usually found in “traditional” readers of Rme marks, but rather it carries a series of HAT (Half-a-TPR) repeats that are rich in aromatic amino acids. Here, we plan to characterize this interaction and investigate the

possibility that other TPR repeat-containing proteins may be involved in sensing arginine methylation. Also, we are investigating the functions of two known effects of Rme marks, called SND1 and TDRD3. Through a combination of mouse work and protein array studies, we have determined that SND1 can likely directly activate

the kinase activity of S6K2, and that TDRD3 can play a role in the DNA damage response.