Regulation of skeletal muscle plasticity by protein arginine methyltransferases

蛋白精氨酸甲基转移酶（PRMT）家族的酶通过其蛋白靶点的甲基化在调节多种细胞事件中发挥关键作用。许多研究表明PRMTs与表型可塑性有关，包括细胞内信号传导、RNA加工、RNA/蛋白质运输、染色质重塑和转录调节的组成部分。最近的研究表明，PRMTs影响骨骼肌的多种细胞过程，如肌生成和葡萄糖代谢。PRMTs对肌肉中运动引起的信号也很敏感。许多被PRMTs甲基化的蛋白质是骨骼肌可塑性的强大调节剂，包括收缩特性、线粒体生物发生、代谢谱和形态。尽管如此，PRMTs介导骨骼肌表型多样性和可塑性的研究尚未得到整合。因此，肌肉中的PRMT生物学是一个新兴的领域，有很大的希望增加我们对调节骨骼肌结构和功能的因素的认识，以及在表型适应条件下这些特征的重塑。在接下来的五年里，我的研究计划努力在PRMTs方面取得重大发现，包括它们在骨骼肌纤维类型和肌肉可塑性条件下的表达、活性和功能。为了实现这一目标，将采用分子生理学解决方案的创新组合，以及一系列相关的实验模型和治疗方法来检查骨骼肌中的PRMTs。这项研究计划的长期目的是维持一个充满活力和富有成效的训练环境，这将增加我们对PRMTs在调节骨骼肌可塑性中的作用的理解，包括控制这些酶的表达和功能的机制。PRMT在哺乳动物生理学中的影响是广泛而重要的，这为骨骼肌PRMT生物学的研究提供了动力和目标，这将远远超出当前提案的持续时间。

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.