O-GlcNAc regulated arginine methylation: a novel paradigm in survival signaling (359.3)

The modification of intracellular proteins by monosaccharides of O-linked β-N-acetylglucosamine (O-GlcNAc) has emerged as a regulator of cytoprotection. In response to cellular stress and injury, O-GlcNAc levels are elevated on numerous proteins. Notably, elevating O-GlcNAc levels before or after the induction of injury is protective in both in vivo and in vitro models. However, the molecular mechanisms by which O-GlcNAc protects injured cells/tissues remain elusive. In this study, we report that protein arginine methyltransferase 1 (PRMT1) is O-GlcNAc modified and associates with the O-GlcNAc transferase (OGT). Our data demonstrates that the association of OGT with PRMT1 inhibits methyltransferase activity. As a consequence, lowering OGT expression leads to an elevation of arginine assymetric dimethylation in vivo. Enhanced arginine assymetric dimethylation is associated with the development of cardiovascular disease, reduced lifespan, and sensitivity to apoptotic stimuli. Consistent with a model in whic...