来自瑞士日内瓦大学的Jörg Morf及其同事发现冷诱导的RNA结合蛋白(CIRP)的周期性积累会受到体温的调控,他们还发现CIRP赋予了昼夜节律振荡器的健壮性。

-2012年10月19日《科学》

中文翻译


【题目】冷诱导的RNA结合蛋白调节节律基因的转录后修饰

【译文】在哺乳动物组织中,节律基因的表达受到局部的振荡器或视交叉上核中生物钟主钟控制的系统信号的调控。本研究发现是受刺激的体温循环而不是外周振荡器,控制纤维母细胞中的冷诱导RNA结合蛋白(CIRP)的节律性表达。反过来,功能缺失性实验表明CIRP是高振幅的节奏基因表达所需的。利用基于生物素-链亲和素的交联和免疫沉淀反应(CLIP),本研究对CIRP结合的RNA进行了全转录组分析,发现了一些编码昼夜节律振荡器蛋白的转录物,包括CLOCK蛋白。此外,在CIRP缺失的纤维母细胞中,CLOCK的含量大大减少。因为在这些细胞中,CLOCK的异位表达提高了节律基因的表达水平,因此我们猜测CIRP通过调节CLOCK的表达水平赋予了昼夜节奏振荡器的健壮性。

英文原稿


[Title]: Cold-Inducible RNA-Binding Protein Modulates Circadian Gene Expression Posttranscriptionally  

[Authors]: Jörg Morf, Guillaume Rey, Kim Schneider, Markus Stratmann, Jun Fujita, Felix Naef, and Ueli Schibler

[Abstract]:In mammalian tissues, circadian gene expression can be driven by local oscillators or systemic signals controlled by the master pacemaker in the suprachiasmatic nucleus. We show that simulated body temperature cycles, but not peripheral oscillators, controlled the rhythmic expression of cold-inducible RNA-binding protein (CIRP) in cultured fibroblasts. In turn, loss-of-function experiments indicated that CIRP was required for high-amplitude circadian gene expression. The transcriptome-wide identification of CIRP-bound RNAs by a biotin-streptavidin–based cross-linking and immunoprecipitation (CLIP) procedure revealed several transcripts encoding circadian oscillator proteins, including CLOCK. Moreover, CLOCK accumulation was strongly reduced in CIRP-depleted fibroblasts. Because ectopic expression of CLOCK improved circadian gene expression in these cells, we surmise that CIRP confers robustness to circadian oscillators through regulation of CLOCK expression.

原文地址

http://www.sciencemag.org/content/338/6105/379.abstract

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