Protein arginine methyltransferase biology in skeletal muscle

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This research proposal is designed to continue our ongoing work in investigating the roles of protein arginine methyltransferases (PRMTs) in determining, maintaining, and remodelling skeletal muscle biology. PRMTs are a family of nine enzymes that catalyze the methylation of arginine residues on target proteins, thereby mediating a diverse set of intracellular functions that are indispensable for survival. Observations made by us and others clearly demonstrate that PRMTs are emerging as important mediators of skeletal muscle phenotype and plasticity. Increases or decreases in physical activity, and dietary alterations such as fasting, elicit significant alterations in skeletal muscle biology. These adaptations are known to occur across a wide range of animal species, including humans. How this takes place is not fully understood. The purpose of this proposal is to investigate what we feel are the most important, cutting-edge research questions that are currently unresolved in understanding PRMT biology in skeletal muscle. We will investigate this by utilizing targeted strategies aimed at examining many steps in the gene expression pathway downstream of PRMTs, as well as broadly by using unbiased transcriptomic and proteomic approaches in muscle responding to acute or chronic cues for muscle plasticity. This will be performed using cell biology, biochemical and molecular approaches in muscle cells in culture, in vivo animal models, and in human participants. The results of our research program will have a significant impact on how we view the importance of PRMTs within the context of the muscle cell, and will allow us to revise our thinking about the cellular and physiological impacts of these enzymes on skeletal muscle structure and function.