Laboratory of RNA Biochemistry, Freie Universität Berlin, Institute of Chemistry and Biochemistry, Takustrasse 6, 14195 Berlin, Germany.
Laboratory of RNA Biochemistry, Freie Universität Berlin, Institute of Chemistry and Biochemistry, Takustrasse 6, 14195 Berlin, Germany.
Mol Cell. 2017 Aug 3;67(3):433-446.e4. doi: 10.1016/j.molcel.2017.06.006. Epub 2017 Jul 6.
The core body temperature of all mammals oscillates with the time of the day. However, direct molecular consequences of small, physiological changes in body temperature remain largely elusive. Here we show that body temperature cycles drive rhythmic SR protein phosphorylation to control an alternative splicing (AS) program. A temperature change of 1°C is sufficient to induce a concerted splicing switch in a large group of functionally related genes, rendering this splicing-based thermometer much more sensitive than previously described temperature-sensing mechanisms. AS of two exons in the 5' UTR of the TATA-box binding protein (Tbp) highlights the general impact of this mechanism, as it results in rhythmic TBP protein levels with implications for global gene expression in vivo. Together our data establish body temperature-driven AS as a core clock-independent oscillator in mammalian peripheral clocks.
所有哺乳动物的核心体温都随一天中的时间而波动。然而，体温的微小生理变化的直接分子后果在很大程度上仍难以捉摸。在这里，我们表明体温循环驱动 SR 蛋白磷酸化的节律性变化，以控制一种选择性剪接（AS）程序。1°C 的温度变化足以诱导一大组功能相关基因的协同剪接转换，使得这种基于剪接的温度计比以前描述的温度感应机制灵敏得多。TATA 结合蛋白（TBP）5'UTR 中两个外显子的剪接突出了这种机制的普遍影响，因为它导致节律性 TBP 蛋白水平，这对体内的整体基因表达有影响。我们的数据共同确立了体温驱动的 AS 作为哺乳动物外周时钟中核心时钟独立振荡器的地位。
