Chaix Amandine, Zarrinpar Amir, Panda Satchidananda
Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037
Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037 Division of Gastroenterology, University of California, San Diego, La Jolla, CA 92093.
J Cell Biol. 2016 Oct 10;215(1):15-25. doi: 10.1083/jcb.201603076.
Circadian clocks are cell-autonomous timing mechanisms that organize cell functions in a 24-h periodicity. In mammals, the main circadian oscillator consists of transcription-translation feedback loops composed of transcriptional regulators, enzymes, and scaffolds that generate and sustain daily oscillations of their own transcript and protein levels. The clock components and their targets impart rhythmic functions to many gene products through transcriptional, posttranscriptional, translational, and posttranslational mechanisms. This, in turn, temporally coordinates many signaling pathways, metabolic activity, organelles' structure and functions, as well as the cell cycle and the tissue-specific functions of differentiated cells. When the functions of these circadian oscillators are disrupted by age, environment, or genetic mutation, the temporal coordination of cellular functions is lost, reducing organismal health and fitness.
昼夜节律时钟是细胞自主的计时机制,以24小时周期组织细胞功能。在哺乳动物中,主要的昼夜节律振荡器由转录-翻译反馈环组成,该反馈环由转录调节因子、酶和支架构成,这些组件能产生并维持自身转录本和蛋白质水平的每日振荡。时钟组件及其靶标通过转录、转录后、翻译和翻译后机制赋予许多基因产物节律性功能。反过来,这又在时间上协调许多信号通路、代谢活动、细胞器的结构和功能,以及细胞周期和分化细胞的组织特异性功能。当这些昼夜节律振荡器的功能因年龄、环境或基因突变而受到破坏时,细胞功能的时间协调就会丧失,从而降低机体的健康和适应性。