puc-header

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

43 Pages Posted: 13 Nov 2019 Publication Status: Published

See all articles by Tom Haltenhof

Tom Haltenhof

Free University of Berlin (FUB) - Laboratory of RNA Biochemistry

Ana Kotte

Free University of Berlin (FUB) - Laboratory of RNA Biochemistry

Francesca de Bortoli

Free University of Berlin (FUB) - Laboratory of RNA Biochemistry

Samira Schiefer

Free University of Berlin (FUB) - Laboratory of RNA Biochemistry

Stefan Meinke

Free University of Berlin (FUB) - Laboratory of RNA Biochemistry

Ann-Kathrin Emmerichs

Free University of Berlin (FUB) - Laboratory of RNA Biochemistry

Kristina Katrin Petermann

Free University of Berlin (FUB) - Laboratory of RNA Biochemistry

Bernd Timmermann

Max-Planck-Institute for Molecular Genetics - Sequencing Core Facility

Andreas Franz

Free University of Berlin (FUB) - Laboratory of RNA Biochemistry

Markus Wahl

Free University of Berlin (FUB) - Laboratory of Structural Biochemistry

Petra Imhof

Free University of Berlin (FUB) - Institute of Theoretical Physics

Marco Preussner

Free University of Berlin (FUB) - Laboratory of RNA Biochemistry

Florian Heyd

Free University of Berlin (FUB) - Laboratory of RNA Biochemistry

More...

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 loop. 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.

Keywords: Body temperature, temperature sensing, alternative splicing, Clk kinase, SR proteins, CIRBP, sex determination

Suggested Citation

Haltenhof, Tom and Kotte, Ana and de Bortoli, Francesca and Schiefer, Samira and Meinke, Stefan and Emmerichs, Ann-Kathrin and Petermann, Kristina Katrin and Timmermann, Bernd and Franz, Andreas and Wahl, Markus and Imhof, Petra and Preussner, Marco and Heyd, Florian, A Conserved Kinase-Based Body Temperature Sensor Globally Controls Alternative Splicing and Gene Expression (November 13, 2019). Available at SSRN: https://ssrn.com/abstract=3486026 or http://dx.doi.org/10.2139/ssrn.3486026
This version of the paper has not been formally peer reviewed.

Tom Haltenhof

Free University of Berlin (FUB) - Laboratory of RNA Biochemistry

Germany

Ana Kotte

Free University of Berlin (FUB) - Laboratory of RNA Biochemistry

Germany

Francesca De Bortoli

Free University of Berlin (FUB) - Laboratory of RNA Biochemistry

Germany

Samira Schiefer

Free University of Berlin (FUB) - Laboratory of RNA Biochemistry

Germany

Stefan Meinke

Free University of Berlin (FUB) - Laboratory of RNA Biochemistry

Germany

Ann-Kathrin Emmerichs

Free University of Berlin (FUB) - Laboratory of RNA Biochemistry

Germany

Kristina Katrin Petermann

Free University of Berlin (FUB) - Laboratory of RNA Biochemistry

Germany

Bernd Timmermann

Max-Planck-Institute for Molecular Genetics - Sequencing Core Facility

Ihnestra├če 63-73
Berlin, 14195
Germany

Andreas Franz

Free University of Berlin (FUB) - Laboratory of RNA Biochemistry

Germany

Markus Wahl

Free University of Berlin (FUB) - Laboratory of Structural Biochemistry ( email )

Van't-Hoff-Str. 8
Berlin, Berlin 14195
Germany

Petra Imhof

Free University of Berlin (FUB) - Institute of Theoretical Physics

Germany

Marco Preussner

Free University of Berlin (FUB) - Laboratory of RNA Biochemistry

Germany

Florian Heyd (Contact Author)

Free University of Berlin (FUB) - Laboratory of RNA Biochemistry ( email )

Germany

Click here to go to Cell.com

Paper statistics

Abstract Views
1,413
Downloads
14
PlumX Metrics