Regulation of skeletal muscle plasticity by protein arginine methyltransferases

点击翻译按钮获取中文摘要

The protein arginine methyltransferase (PRMT) family of enzymes play key roles in regulating a multitude of cellular events via methylation of their protein targets. Numerous studies have implicated PRMTs in phenotypic plasticity, including components of intracellular signaling, RNA processing, RNA/protein trafficking, chromatin remodeling, and transcriptional regulation. Recent investigations have revealed that PRMTs influence diverse cellular processes in skeletal muscle, such as myogenesis and glucose metabolism. PRMTs are also sensitive to exercise-induced signals in muscle. Many proteins that are methylated by PRMTs are extremely powerful modifiers of skeletal muscle plasticity, including contractile characteristics, mitochondrial biogenesis, metabolic profile, and morphology. Despite this however, the study of PRMTs in mediating phenotypic diversity and plasticity in skeletal muscle has not yet coalesced. Thus, PRMT biology in muscle is an emerging field with great promise to increase our knowledge of the factors regulating skeletal muscle structure and function, as well as the remodeling of these characteristics during conditions of phenotypic adaptation. Over the next five years, my research plan endeavours to make key discoveries on PRMTs, including their expression, activity, and function in skeletal muscle fiber types and during conditions of muscle plasticity. To accomplish this, an innovative combination of molecular physiological solutions, as well as an array of relevant experimental models and treatments to examine PRMTs in skeletal muscle will be employed. The long-term purpose of this research program is to perpetuate a vibrant and productive training environment that will increase our understanding of the roles of PRMTs in mediating skeletal muscle plasticity, including the mechanisms governing the expression and function of these enzymes. The influence of PRMTs in mammalian physiology is broad and important, which provides the motivation and objectives to fulfill a research program focused on PRMT biology in skeletal muscle that will go well beyond the duration of this current proposal.