Gotic Ivana, Omidi Saeed, Fleury-Olela Fabienne, Molina Nacho, Naef Felix, Schibler Ueli
Department of Molecular Biology, University of Geneva, CH-1211 Geneva 4, Switzerland;
The Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland.
Genes Dev. 2016 Sep 1;30(17):2005-17. doi: 10.1101/gad.287094.116. Epub 2016 Sep 15.
In mammals, body temperature fluctuates diurnally around a mean value of 36°C-37°C. Despite the small differences between minimal and maximal values, body temperature rhythms can drive robust cycles in gene expression in cultured cells and, likely, animals. Here we studied the mechanisms responsible for the temperature-dependent expression of cold-inducible RNA-binding protein (CIRBP). In NIH3T3 fibroblasts exposed to simulated mouse body temperature cycles, Cirbp mRNA oscillates about threefold in abundance, as it does in mouse livers. This daily mRNA accumulation cycle is directly controlled by temperature oscillations and does not depend on the cells' circadian clocks. Here we show that the temperature-dependent accumulation of Cirbp mRNA is controlled primarily by the regulation of splicing efficiency, defined as the fraction of Cirbp pre-mRNA processed into mature mRNA. As revealed by genome-wide "approach to steady-state" kinetics, this post-transcriptional mechanism is widespread in the temperature-dependent control of gene expression.
在哺乳动物中，体温围绕36°C - 37°C的平均值昼夜波动。尽管最小值和最大值之间差异很小，但体温节律可驱动培养细胞以及可能在动物体内的基因表达产生强劲的循环。在此，我们研究了负责冷诱导RNA结合蛋白（CIRBP）温度依赖性表达的机制。在暴露于模拟小鼠体温循环的NIH3T3成纤维细胞中，Cirbp mRNA的丰度振荡约三倍，就像在小鼠肝脏中一样。这种每日mRNA积累循环直接受温度振荡控制，不依赖于细胞的生物钟。在此我们表明，Cirbp mRNA的温度依赖性积累主要受剪接效率调节的控制，剪接效率定义为加工成成熟mRNA的Cirbp前体mRNA的比例。如全基因组“达到稳态”动力学所揭示的，这种转录后机制在基因表达的温度依赖性控制中广泛存在。
