A Conserved Kinase-Based Body-Temperature Sensor Globally Controls Alternative 
Splicing and Gene Expression

Haltenhof, Tom; Kotte, Ana; De Bortoli, Francesca; Schiefer, Samira; Meinke, Stefan; Emmerichs, Ann-Kathrin; Petermann, Kristina Katrin; Timmermann, Bernd; Imhof, Petra; Franz, Andreas; Loll, Bernhard; Wahl, Markus C.; Preußner, Marco; Heyd , Florian

doi:10.1016/j.molcel.2020.01.028

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A Conserved Kinase-Based Body-Temperature Sensor Globally Controls Alternative Splicing and Gene Expression

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Timmermann, Bernd
Sequencing (Head: Bernd Timmermann), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Citation

Haltenhof, T., Kotte, A., De Bortoli, F., Schiefer, S., Meinke, S., Emmerichs, A.-K., et al. (2020). A Conserved Kinase-Based Body-Temperature Sensor Globally Controls Alternative Splicing and Gene Expression. Molecular Cell, 78(1), 57-69. doi:10.1016/j.molcel.2020.01.028.

Cite as: https://hdl.handle.net/21.11116/0000-0005-FABF-B

Abstract

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.