Douris Nicholas, Green Carla B
Department of Biology, University of Virginia, Charlottesville, VA 22904, USA.
Ann Med. 2008;40(8):622-6. doi: 10.1080/07853890802084878.
The circadian clock is a conserved internal timekeeping mechanism that controls many aspects of physiology and behavior via the rhythmic expression of many genes. One of these rhythmic genes, Nocturnin, encodes a deadenylase--a ribonuclease that specifically removes the poly(A) tails from mRNAs. This enzyme is expressed at high levels during the night in a number of tissues in mammals and has recently been implicated in circadian control of metabolism. Targeted ablation of this gene in mice results in resistance to hepatic steatosis and diet-induced obesity. Nocturnin appears to exert rhythmic posttranscriptional control of genes necessary for metabolic functions including nutrient absorption, glucose/insulin sensitivity, and lipid storage. In the Western world and many developing countries, overnutrition--the 'obesity epidemic' suggests that the ability to sequester fat stores in times of plenty is no longer advantageous to our survival. Understanding the role that the circadian clock plays in controlling these metabolic processes is important in treatment and eventual eradication of this public health crisis.
昼夜节律时钟是一种保守的内部计时机制，它通过许多基因的节律性表达来控制生理和行为的许多方面。这些节律基因之一，夜蛋白（Nocturnin），编码一种去腺苷酸化酶——一种特异性去除mRNA上的聚腺苷酸尾巴的核糖核酸酶。这种酶在哺乳动物的许多组织中夜间高水平表达，最近被认为参与了代谢的昼夜节律控制。在小鼠中靶向敲除该基因会导致对肝脂肪变性和饮食诱导的肥胖具有抗性。夜蛋白似乎对包括营养吸收、葡萄糖/胰岛素敏感性和脂质储存在内的代谢功能所需基因进行节律性转录后调控。在西方世界和许多发展中国家，营养过剩——“肥胖流行”表明，在食物充足时储存脂肪的能力对我们的生存不再具有优势。了解昼夜节律时钟在控制这些代谢过程中所起的作用对于治疗并最终消除这一公共卫生危机至关重要。
