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生物节律的新发现---不仅仅调控基因的转录

发布者:鑫达医学翻译 发布时间:2012-10-20阅读:

    生物钟影响着着人类健康的方方面面,近年来科学家对它的分子网络结构进行了深入的研究。由于生物钟对疾病的发生发展以及包括免疫反应,代谢和衰老等生命活动均有调控作用,理解生物钟如何控制其调控的下游过程具有广泛的临床意义。哺乳动物的生物钟的主要分子组成以及其调控网络已经被人们充分认识,但是一个关键的问题依然没有解决:这些基本的分子如何把这些复杂但又组织完善的调控网络转化为有条不紊的生命活动?今天的科学杂志刊发了一个美国团队((Koike, N., S. H. Yoo, et al. (2012).     "Transcriptional Architecture and Chromatin Landscape of the Core Circadian Clock in Mammals." Science. http://www.sciencemag.org/content/338/6105/349.full)和一个瑞士团队(Morf, J., G. Rey, et al. (2012). "Cold-Inducible RNA-Binding Protein Modulates Circadian Gene Expression Posttranscriptionally." Science. http://www.sciencemag.org/content/338/6105/379.full)从转录后调控水平对这一问题进行探索的成果,前者利用全基因组筛选的方法,后者对特定因子进行功能表征,发现生物钟对mRNA转录后调控有着重要影响。Koike等在全基因组水平监测了哺乳动物生物钟直接调控的靶标随着时间变化的情况,意外发现受调控的靶标的变化并不引起一些稳定存在的mRNA量的变化。Morf 等也观察到了这种现象,并鉴定出一个参与生物钟转录后调控的因子---冷诱导RNA结合蛋白(cold-inducible RNA-binding protein ,CIRP),并对它的调控效应进行了表征。

Science 19 October 2012: Vol. 338 no. 6105 pp. 338-340 DOI: 10.1126/science.1230008PERSPECTIVE
CIRCADIAN RHYTHMS
Circadian Surprise—It's Not All About Transcription
Colleen J. Doherty1,  Steve A. Kay2
+Author Affiliations
1Center for Chronobiology, University of California, San Diego, La Jolla, CA 92093–0116, USA.
2Dana and David Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA 90089, USA.

The integral role of the circadian clock in numerous aspects of health has prompted extensive study of the molecular architecture of clock networks. Understanding how the clock controls downstream processes has widespread clinical impacts, as it affects many diseases and biological processes including immune responses, metabolism, and aging (1–3). The primary molecular components of the mammalian oscillator and a detailed understanding of the regulatory interactions among them have been well characterized (4,5). However, one critical question remains unanswered: How do the cogs of this clock translate the rhythmic regulatory relationship among themselves into the plethora of outputs that are under circadian control? On pages 349 and 379 of this issue, Koike et al. (6) and Morfet al. (7) investigate this problem from opposite ends of the spectrum—a genome-wide discovery approach and the functional characterization of a specific factor, respectively—yet they converge to emphasize the importance of posttranscriptional regulation of messenger RNA (mRNA) levels on the clock.

Although a few specific connections have been identified (8–10), the direct global orchestration that occurs between transcriptional loops of the clock and the myriad of circadian-regulated phenotypic responses has been elusive. Koike et al. mapped in both time and genome-space the targets of many transcriptional components of the mammalian circadian clock. As they compared the regulation of these targets to their expression by RNA sequencing, the authors found a surprising disconnect between the nascent transcripts and the amounts of steady-state mRNA. This implication of posttranscriptional control is echoed by Morf et al., who identified a factor involved in circadian posttranscriptional regulation, cold-inducible RNA-binding protein (CIRP), and characterized its regulatory effects on the clock.
 


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