Body Temperature Cycles Control Rhythmic Alternative Splicing in Mammals

5 years ago

Body Temperature Cycles Control Rhythmic Alternative Splicing in Mammals

The core body temperature of all mammals oscillates with the time of the day. However, direct molecular consequences of small, physiological changes in body temperature remain largely elusive. Here we show that body temperature cycles drive rhythmic SR protein phosphorylation to control an alternative splicing (AS) program. A temperature change of 1°C is sufficient to induce a concerted splicing switch in a large group of functionally related genes, rendering this splicing-based thermometer much more sensitive than previously described temperature-sensing mechanisms. AS of two exons in the 5′ UTR of the TATA-box binding protein (Tbp) highlights the general impact of this mechanism, as it results in rhythmic TBP protein levels with implications for global gene expression in vivo. Together our data establish body temperature-driven AS as a core clock-independent oscillator in mammalian peripheral clocks.

Graphical abstract

Teaser

Preußner et al. show that temperature changes of 1°C control alternative splicing of many mammalian exons through SR protein phosphorylation. This is the most sensitive cellular thermometer described until now, resulting in rhythmic alternative splicing through circadian body temperature cycles.

Publisher URL: www.sciencedirect.com/science

DOI: S1097276517304082