Regulation of skeletal muscle plasticity by protein arginine methyltransferases

蛋白质精氨酸甲基转移酶（PRMT）家族的酶通过其蛋白质靶标的甲基化在调节多种细胞事件中起关键作用。许多研究表明PRMT参与表型可塑性，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控的组分。最近的研究表明，PRMT影响骨骼肌中的多种细胞过程，如肌生成和葡萄糖代谢。PRMT也对肌肉中运动诱导的信号敏感。被PRMT甲基化的许多蛋白质是骨骼肌可塑性的极其强大的修饰剂，包括收缩特性、线粒体生物发生、代谢谱和形态。然而，尽管如此，PRMTs在介导骨骼肌表型多样性和可塑性方面的研究尚未合并。因此，肌肉中的PRMT生物学是一个新兴的领域，具有很大的希望，以增加我们的知识的因素，调节骨骼肌的结构和功能，以及重塑这些特征的条件下的表型适应。在接下来的五年里，我的研究计划致力于对PRMT进行关键发现，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PRMT。这项研究计划的长期目的是保持一个充满活力和富有成效的训练环境，这将增加我们对PRMT在介导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，这提供了动机和目标，以实现专注于骨骼肌中PRMT生物学的研究计划，该计划将远远超出本提案的持续时间。

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.