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A conserved kinase-based body temperature sensor globally controls alternative splicing and gene expression

ABSTRACT: Homoeothermic 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 remains 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE143872 | GEO | 2020/02/14

REPOSITORIES: GEO

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Project description:Gould2011 - Temperature Sensitive Circadian Clock This model is a temperature sensitive version of Pokhilko et al. 2010 (PMID: 20865009), which is BIOMD0000000273 in BioModels. This model is described in the article: Network balance via CRY signalling controls the Arabidopsis circadian clock over ambient temperatures. Gould PD, Ugarte N, Domijan M, Costa M, Foreman J, Macgregor D, Rose K, Griffiths J, Millar AJ, Finkenstädt B, Penfield S, Rand DA, Halliday KJ, Hall AJ. Mol. Syst. Biol. 2013; 9: 650 Abstract: Circadian clocks exhibit 'temperature compensation', meaning that they show only small changes in period over a broad temperature range. Several clock genes have been implicated in the temperature-dependent control of period in Arabidopsis. We show that blue light is essential for this, suggesting that the effects of light and temperature interact or converge upon common targets in the circadian clock. Our data demonstrate that two cryptochrome photoreceptors differentially control circadian period and sustain rhythmicity across the physiological temperature range. In order to test the hypothesis that the targets of light regulation are sufficient to mediate temperature compensation, we constructed a temperature-compensated clock model by adding passive temperature effects into only the light-sensitive processes in the model. Remarkably, this model was not only capable of full temperature compensation and consistent with mRNA profiles across a temperature range, but also predicted the temperature-dependent change in the level of LATE ELONGATED HYPOCOTYL, a key clock protein. Our analysis provides a systems-level understanding of period control in the plant circadian oscillator. This model is hosted on BioModels Database and identified by: BIOMD0000000564. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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A conserved kinase-based body temperature sensor globally controls alternative splicing and gene expression

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