Homeothermic organisms maintain their core body temperature in a narrow, tightly controlled range. Whether and how subtle circadian oscillations or disease-associated changes in core body temperature are sensed and integrated in gene expression programs remain elusive. Furthermore, a thermo-sensor capable of sensing the small temperature differentials leading to temperature-dependent sex determination (TSD) in poikilothermic reptiles has not been identified. Here, we show that the activity of CDC-like kinases (CLKs) is highly responsive to physiological temperature changes, which is conferred by structural rearrangements within the kinase activation segment. Lower body temperature activates CLKs resulting in strongly increased phosphorylation of SR proteins in vitro and in vivo. This globally controls temperature-dependent alternative splicing and gene expression, with wide implications in circadian, tissue-specific, and disease-associated settings. This temperature sensor is conserved across evolution and adapted to growth temperatures of diverse poikilotherms. The dynamic temperature range of reptilian CLK homologs suggests a role in TSD.

中文翻译：

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一个保守的基于激酶的体温传感器全局控制替代剪接和基因表达。

恒温生物将其核心体温维持在狭窄且严格控制的范围内。人体体温的细微昼夜节律振荡或与疾病相关的变化是否被感测到以及如何被整合到基因表达程序中仍然难以捉摸。此外，尚未发现能够感测导致温热爬行动物中温度依赖性性别确定（TSD）的微小温差的热传感器。在这里，我们显示CDC样激酶（CLKs）的活性对生理温度的变化高度敏感，这是由激酶激活区段内的结构重排所赋予的。较低的体温会激活CLK，从而在体外和体内大大增强SR蛋白的磷酸化。这全局控制温度依赖的替代剪接和基因表达，在昼夜节律，组织特异性和疾病相关环境中具有广泛的意义。该温度传感器在整个进化过程中均得到保存，并适应各种Poikilotherm的生长温度。爬虫类CLK同源物的动态温度范围暗示了TSD的作用。