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

Area of Science:

• Molecular Biology
• Physiology
• Genetics

Background:

• Homeothermic organisms maintain a narrow core body temperature.
• Mechanisms sensing subtle temperature changes for gene expression are largely unknown.
• A thermo-sensor for temperature-dependent sex determination (TSD) in reptiles remains unidentified.

Purpose of the Study:

• To identify a thermo-sensor responsive to physiological temperature fluctuations.
• To investigate the role of CDC-like kinases (CLKs) in temperature sensing.
• To explore the implications of CLK-mediated temperature sensing in gene expression and TSD.

Main Methods:

• In vitro and in vivo assays to measure CLK activity and SR protein phosphorylation.
• Structural analysis of CLK activation segments.
• Comparative analysis of CLK homologs across species.

Main Results:

• CLK activity is highly sensitive to physiological temperature changes due to structural rearrangements.
• Lower temperatures activate CLKs, increasing SR protein phosphorylation.
• This process globally controls temperature-dependent alternative splicing and gene expression.

Conclusions:

• CLKs function as a conserved temperature sensor across evolution.
• This mechanism influences circadian rhythms, tissue-specific gene expression, and disease states.
• Reptilian CLK homologs' temperature sensitivity suggests a role in TSD.