Translational Suppression of Atrophic Regulators by MicroRNA-23a Integrates Resistance to Skeletal Muscle Atrophy
Translational Suppression of Atrophic Regulators by MicroRNA-23a Integrates Resistance to Skeletal Muscle Atrophy
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DOI：
10.1074/jbc.m111.271270
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发表时间：
2011-11-04
影响因子：
4.8
通讯作者：
Akimoto, Takayuki
中科院分区：
文献类型：
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作者：
Wada, Shogo;Kato, Yoshio;Akimoto, Takayuki
肌肉萎缩是由加速的蛋白质降解引起的，并且在许多病理状态下发生。两种肌肉特异性泛素连接酶，MAFbx/atrogin-1和肌肉环指蛋白1（MuRF 1），在肌肉萎缩期间显著诱导并介导萎缩相关蛋白降解。阻断这两种泛素连接酶的表达提供了针对肌肉萎缩的保护。在这里，我们报告了miR-23 a以3 '-UTR依赖性方式抑制MAFbx/atrogin-1和MuRF 1的翻译。miR-23 a的异位表达足以在体外和体内保护肌肉免于萎缩。此外，miR-23 a转基因小鼠对糖皮质激素诱导的骨骼肌萎缩表现出抵抗力。这些数据表明，单一miRNA对多种调节因子的抑制在成体组织中可能具有显著的后果。
Muscle atrophy is caused by accelerated protein degradation and occurs in many pathological states. Two muscle-specific ubiquitin ligases, MAFbx/atrogin-1 and muscle RING-finger 1 (MuRF1), are prominently induced during muscle atrophy and mediate atrophy-associated protein degradation. Blocking the expression of these two ubiquitin ligases provides protection against muscle atrophy. Here we report that miR-23a suppresses the translation of both MAFbx/atrogin-1 and MuRF1 in a 3'-UTR-dependent manner. Ectopic expression of miR-23a is sufficient to protect muscles from atrophy in vitro and in vivo. Furthermore, miR-23a transgenic mice showed resistance against glucocorticoid-induced skeletal muscle atrophy. These data suggest that suppression of multiple regulators by a single miRNA can have significant consequences in adult tissues.