Chen Xi, Wang Kehui, Chen Jiangning, Guo Jigang, Yin Yuan, Cai Xing, Guo Xing, Wang Guoqiang, Yang Rong, Zhu Lingyun, Zhang Yan, Wang Jin, Xiang Yang, Weng Chunyue, Zen Ke, Zhang Junfeng, Zhang Chen-Yu
Jiangsu Diabetes Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China.
J Biol Chem. 2009 Feb 20;284(8):5362-9. doi: 10.1074/jbc.M807523200. Epub 2008 Dec 10.
UCP2 and UCP3, two novel uncoupling proteins, are important regulators of energy expenditure and thermogenesis in various organisms. The striking disparity between UCP2 mRNA and protein levels in muscle tissues prompted initial speculation that microRNAs are implicated in the regulatory pathway of UCP2. We found, for the first time, that the repression of UCP2 expression in cardiac and skeletal muscle resulted from its targeting by a muscle-specific microRNA, miR-133a. Moreover, our findings illustrate a novel function of UCP2 as a brake for muscle development. We also show that MyoD can remove the braking role of UCP2 via direct up-regulation of miR-133a during myogenic differentiation. Taken together, our current work delineates a novel regulatory network employing MyoD, microRNA, and uncoupling proteins to fine-tune the balance between muscle differentiation and proliferation during myogenesis.
解偶联蛋白2（UCP2）和解偶联蛋白3（UCP3）这两种新型解偶联蛋白，是多种生物体能量消耗和产热的重要调节因子。肌肉组织中UCP2信使核糖核酸（mRNA）水平与蛋白质水平之间存在显著差异，这引发了最初的推测，即微小核糖核酸（microRNA）参与了UCP2的调控途径。我们首次发现，心肌和骨骼肌中UCP2表达的抑制是由一种肌肉特异性微小核糖核酸miR - 133a靶向作用所致。此外，我们的研究结果揭示了UCP2作为肌肉发育制动器的新功能。我们还表明，在成肌分化过程中，肌分化抗原（MyoD）可通过直接上调miR - 133a来消除UCP2的制动作用。综上所述，我们目前的工作描绘了一个新的调控网络，该网络利用MyoD、微小核糖核酸和解偶联蛋白在肌生成过程中微调肌肉分化与增殖之间的平衡。
