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Jun 11, 2019

Seminar - Body temperature controlled kinase activity: from rhythmic alternative splicing in mammals to sex determination in reptiles (Speaker: Professor Dr. Florian Heyd)

Professor Dr. Florian Heyd
Professor of RNA Biochemistry
Free University of Berlin, Germany

Date: Tuesday,11-June-2019
Time: 4:00 p.m.
Venue: Seminar Room 2, G/F, Jockey Club Building for Interdisciplinary Research
5 Sassoon Road, Pokfulam, Hong Kong

Summary:
Endothermic organisms maintain their core body temperature in a narrow range with subtle circadian oscillation, tissue-specific differences or alterations in pathological conditions. In contrast, ectotherms adapt to the external temperature, which, in some reptiles, induces temperature-dependent sex determination (TSD). However, a molecular thermometer that is able to sense small changes in temperature has remained elusive. Here Professor Heyd’s group show that the activity of CDC-like kinases (CLKs) is highly responsive to physiological temperature changes. Lower body temperature activates CLKs, resulting in strongly increased phosphorylation of SR-repeats, with wide implications for circadian, tissue-specific and disease-associated alternative splicing and pre-mRNA processing. Temperature sensitivity is conferred by conformational changes, which at higher temperature, blocks substrate access to the active center. CLK temperature-sensitivity is conserved across evolution and adapted to growth temperatures of diverse ectotherms. Interestingly, the dynamic temperature range of reptilian CLK homologs suggests a role as molecular thermometer controlling TSD.

 

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