Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada.
School of Kinesiology and Health Studies, Queen's University, Kingston, Ontario, Canada.
J Appl Physiol (1985). 2019 Sep 1;127(3):867-880. doi: 10.1152/japplphysiol.00142.2019. Epub 2019 Aug 1.
Protein arginine methyltransferases (PRMTs) are a family of enzymes that catalyze the methylation of arginine residues on target proteins. While dysregulation of PRMTs has been documented in a number of the most prevalent diseases, our understanding of PRMT biology in human skeletal muscle is limited. This study served to address this knowledge gap by exploring PRMT expression and function in human skeletal muscle in vivo and characterizing PRMT biology in response to acute and chronic stimuli for muscle plasticity. Fourteen untrained, healthy men performed one session of sprint interval exercise (SIE) before completing four bouts of SIE per week for 6 wk as part of a sprint interval training (SIT) program. Throughout this time course, multiple muscle biopsies were collected. We found that at basal, resting conditions PRMT1, PRMT4, PRMT5, and PRMT7 were the most abundantly expressed PRMT mRNAs in human quadriceps muscle. Additionally, the broad subcellular distribution pattern of PRMTs suggests methyltransferase activity throughout human myofibers. A spectrum of PRMT-specific inductions, and decrements, in expression and activity were observed in response to acute and chronic cues for muscle plasticity. In conclusion, our findings demonstrate that PRMTs are present and active in human skeletal muscle in vivo and that there are distinct, enzyme-specific responses and adaptations in PRMT biology to acute and chronic stimuli for muscle plasticity. This work advances our understanding of this critical family of enzymes in humans. This is the first report of protein arginine methyltransferase (PRMT) biology in human skeletal muscle in vivo. We observed that PRMT1, -4, -5, and -7 were the most abundant PRMT mRNAs in human muscle and that PRMT proteins exhibited a broad subcellular localization that included myonuclear, cytosolic, and sarcolemmal compartments. Acute exercise and chronic training evoked PRMT-specific alterations in expression and activity. This study reveals a hitherto unknown complexity to PRMT biology in human muscle.
蛋白质精氨酸甲基转移酶（PRMTs）是一类酶，可催化靶蛋白精氨酸残基的甲基化。虽然 PRMTs 的失调已在许多最常见的疾病中得到证实，但我们对人类骨骼肌中 PRMT 生物学的理解是有限的。本研究通过探索体内人类骨骼肌中 PRMT 的表达和功能，并对肌肉可塑性的急性和慢性刺激做出反应来表征 PRMT 生物学，以解决这一知识空白。14 名未经训练的健康男性在完成 Sprint Interval Training（SIT）计划的 6 周内每周进行 4 次 Sprint Interval Exercise（SIE）之前，完成了一次 SIE 运动。在此期间，采集了多份肌肉活检。我们发现，在基础、休息状态下，PRMT1、PRMT4、PRMT5 和 PRMT7 是人体四头肌中表达最丰富的 PRMT mRNA。此外，PRMTs 的广泛亚细胞分布模式表明，甲基转移酶活性存在于人体肌纤维中。在响应肌肉可塑性的急性和慢性线索时，观察到 PRMT 表达和活性的特定诱导和减少。总之，我们的研究结果表明，PRMTs存在于体内人类骨骼肌中，并且对肌肉可塑性的急性和慢性刺激有独特的、酶特异性的反应和适应。这一工作增进了我们对人类这一关键酶家族的理解。这是首次在体内报告人类骨骼肌中的蛋白质精氨酸甲基转移酶（PRMT）生物学。我们观察到 PRMT1、-4、-5 和-7 是人类肌肉中最丰富的 PRMT mRNA，并且 PRMT 蛋白表现出广泛的亚细胞定位，包括核膜、胞质和肌膜间隙。急性运动和慢性训练引起 PRMT 表达和活性的特异性改变。本研究揭示了人类肌肉中 PRMT 生物学迄今为止未知的复杂性。
