红细胞中近日节律系统的非转录调控机制研究

The regulation mechanism of gene expression from DNA to protein is of great significance to physiological and pathological processes of the organisms. It is widely accepted that the classic regulation mechanism in mammals on the molecular clock is the transcription and translation feedback loop. Until recently, it has been reported confirmed that the non-transcription and translation regulation mechanism, which exist in the circadian rhythm system of some most simplest prokaryotes, exists in human erythrocytes. We did preliminary experiment to explore whether the circadian rhythm in erythrocytes could be entrained by the light-dark cycle, and our results found the red blood cell was able to accept the optical signals, suggesting that there is a link between the non-transcription and translation system and the transcription and translation feedback loop, in which they could interact each other. In this study, we are planning to study the rhythmicity of Coenzyme I and coenzyme II, and their roles in the redox system, we are also going to investigate the zeitgeber between the transcription and translation feedback loop and the non-transcription and translation system, and their pathways to interact. This research is designed to reveal the mechanisms on the interaction between non-transcription and translation system and circadian rhythmicity of redox system or transcription and translation feedback loop, and eventually to clarify the significance of the existence of non-transcription and translation system in mammals.

从DNA到蛋白质的基因表达的调控机制，对生物体的生理、病理过程都具有重要的意义。在哺乳动物中，人们一直认为分子钟的转录翻译反馈是调控近日节律经典的机制。而存在于一些最简单的原核生物近日节律系统中的非转录翻译调控机制，直到最近有被报道证实其也存在于人类的红细胞中。我们就红细胞的节律是否能够受到光暗循环的导引进行了前期实验，结果初步发现红细胞能够接受光信号，这就提示非转录翻译调控系统与转录翻译反馈环路之间具有联系，并且能够相互影响。本研究将在此基础上进一步研究在无转录翻译调控情况下辅酶I、辅酶II的节律性以及其对氧化还原系统的作用，同时研究联系转录翻译调控系统与非转录翻译调控系统的授时因子和相互作用的通路。以期探明非转录翻译调控系统与红细胞氧化还原节律系统、转录翻译反馈环路之间的相互作用机制；并最终阐明生物节律的非转录翻译调控系统在哺乳动物存在的意义。

为了研究红细胞中近日节律系统的非转录调控机制，本项目主要从无转录翻译调控情况下辅酶I和辅酶II 的节律性、辅酶I和辅酶II 对氧化还原系统的作用、以及其中授时因子的作用进行了研究，发现小鼠红细胞中辅酶I和辅酶II具有自发的节律性，其参与了非转录调控对PRX2的调节，并得到了一批与非转录调控相关的蛋白，我们还在研究中发现长期的睡眠不足和游戏使精神处于兴奋状态对节律系统非转录调控具有明显的影响，但非转录调控的进行似乎与信号通路的关系不大，反而是与授时因子的结构、以及能量代谢有关。这为我们对非转录调控的研究提供了一条新的思路。