CARM1 转录组和精氨酸甲基化蛋白质组介导骨骼肌整体生物学。
The CARM1 transcriptome and arginine methylproteome mediate skeletal muscle integrative biology.
机构信息
Department of Kinesiology, McMaster University, Hamilton, ON, L8S 4L8, Canada.
Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA, 90089, USA.
出版信息
Mol Metab. 2022 Oct;64:101555. doi: 10.1016/j.molmet.2022.101555. Epub 2022 Jul 21.
OBJECTIVE
Coactivator-associated arginine methyltransferase 1 (CARM1) catalyzes the methylation of arginine residues on target proteins to regulate critical processes in health and disease. A mechanistic understanding of the role(s) of CARM1 in skeletal muscle biology is only gradually emerging. The purpose of this study was to elucidate the function of CARM1 in regulating the maintenance and plasticity of skeletal muscle.
METHODS
We used transcriptomic, methylproteomic, molecular, functional, and integrative physiological approaches to determine the specific impact of CARM1 in muscle homeostasis.
RESULTS
Our data defines the occurrence of arginine methylation in skeletal muscle and demonstrates that this mark occurs on par with phosphorylation and ubiquitination. CARM1 skeletal muscle-specific knockout (mKO) mice displayed altered transcriptomic and arginine methylproteomic signatures with molecular and functional outcomes confirming remodeled skeletal muscle contractile and neuromuscular junction characteristics, which presaged decreased exercise tolerance. Moreover, CARM1 regulates AMPK-PGC-1α signalling during acute conditions of activity-induced muscle plasticity.
CONCLUSIONS
This study uncovers the broad impact of CARM1 in the maintenance and remodelling of skeletal muscle biology.
目的
共激活因子相关精氨酸甲基转移酶 1（CARM1）催化靶蛋白精氨酸残基的甲基化，以调节健康和疾病中的关键过程。CARM1 在骨骼肌生物学中的作用机制的理解只是逐渐出现。本研究的目的是阐明 CARM1 在调节骨骼肌维持和可塑性中的功能。
方法
我们使用转录组学、甲基蛋白质组学、分子、功能和综合生理学方法来确定 CARM1 在肌肉动态平衡中的具体作用。
结果
我们的数据定义了精氨酸甲基化在骨骼肌中的发生，并表明该标记与磷酸化和泛素化同时发生。CARM1 骨骼肌特异性敲除（mKO）小鼠显示出改变的转录组和精氨酸甲基蛋白质组特征，分子和功能结果证实了重塑的骨骼肌收缩和神经肌肉接头特征，预示着运动耐力降低。此外，CARM1 在活动诱导的肌肉可塑性的急性条件下调节 AMPK-PGC-1α 信号。
结论
这项研究揭示了 CARM1 在维持和重塑骨骼肌生物学中的广泛影响。
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