The emergence of protein arginine methyltransferases in skeletal muscle and metabolic disease

Abstract

Protein arginine methyltransferases (PRMTs) are a family of enzymes that catalyze the methylation of arginine residues on target proteins and thus alter the stability, localization, or activity of the substrate. In doing so, PRMTs mediate a variety of intracellular functions that are essential for survival. Additionally, PRMT dysregulation is involved in a number of the most prevalent health disorders, including cancer and neurodegenerative and cardiovascular diseases, as well as in the aging process. Investigations of PRMT biology in skeletal muscle cells began in 2002, and since then these enzymes have emerged as regulators of skeletal muscle phenotype determination, maintenance, and remodeling. Specifically, more recent in vivo studies have revealed that PRMTs impact multiple aspects of skeletal muscle biology, including satellite cell function and phenotypic plasticity in response to exercise and disuse. Skeletal muscle plays critically important roles in regulating whole body metabolism, and recent investigations have also begun elucidating PRMT expression and function under conditions of metabolic dysfunction. The goals of this review are to 1) summarize the literature on PRMT biology in skeletal muscle with a particular emphasis on the in vivo evidence and 2) survey PRMTs in metabolic disorders, namely, obesity and type 2 diabetes mellitus. We also identify notable knowledge gaps therein and present opportunities to further expand our understanding of these enzymes so critical to health and disease.