Institute of Chemistry and Biochemistry, Laboratory of RNA Biochemistry, Freie Universität Berlin, Berlin, Germany.
Omiqa Bioinformatics, Berlin, Germany.
EMBO Rep. 2020 Dec 3;21(12):e51369. doi: 10.15252/embr.202051369. Epub 2020 Nov 2.
Mammalian body temperature oscillates with the time of the day and is altered in diverse pathological conditions. We recently identified a body temperature-sensitive thermometer-like kinase, which alters SR protein phosphorylation and thereby globally controls alternative splicing (AS). AS can generate unproductive variants which are recognized and degraded by diverse mRNA decay pathways-including nonsense-mediated decay (NMD). Here we show extensive coupling of body temperature-controlled AS to mRNA decay, leading to global control of temperature-dependent gene expression (GE). Temperature-controlled, decay-inducing splicing events are evolutionarily conserved and pervasively found within RNA-binding proteins, including most SR proteins. AS-coupled poison exon inclusion is essential for rhythmic GE of SR proteins and has a global role in establishing temperature-dependent rhythmic GE profiles, both in mammals under circadian body temperature cycles and in plants in response to ambient temperature changes. Together, these data identify body temperature-driven AS-coupled mRNA decay as an evolutionary ancient, core clock-independent mechanism to generate rhythmic GE.
哺乳动物的体温随一天中的时间而波动，并在各种病理条件下发生改变。我们最近发现了一种体温敏感的类激酶，它改变了 SR 蛋白的磷酸化，从而全局控制选择性剪接（AS）。AS 可以产生无功能的变体，这些变体被多种 mRNA 降解途径识别和降解，包括无意义介导的降解（NMD）。在这里，我们展示了体温控制的 AS 与 mRNA 降解的广泛偶联，从而实现了对温度依赖性基因表达（GE）的全局控制。受体温控制、诱导降解的剪接事件在进化上是保守的，并且在包括大多数 SR 蛋白在内的 RNA 结合蛋白中普遍存在。AS 偶联的“毒性外显子”包含对于 SR 蛋白的节律性 GE 是必需的，并且在哺乳动物的昼夜体温循环和植物对环境温度变化的反应中，都具有全局作用，以建立温度依赖性的节律性 GE 模式。总之，这些数据表明，由体温驱动的 AS 偶联的 mRNA 降解是一种古老的、核心时钟独立的机制，可产生节律性的 GE。
