Thermosensitive alternative splicing senses and mediates temperature adaptation in Drosophila

Circadian rhythms are generated by the cyclic transcription, translation and degradation of clock genes, including timeless (tim). Currently, little is known about the mechanisms by which the circadian clock senses and adapts to temperature changes. Here we show that temperature dramatically changes the splicing pattern of tim. We found that at 18C TIM protein levels are diminished due to the induction of two cold-specific splicing isoforms (tim-cold and tim-shortu0026cold). At 29C, another isoform, tim-Medium is strongly upregulated. We found that this isoform switching mechanism allows flies to regulate the levels and activity of TIM by setting miRNA-dependent thresholds for expression as well as by expressing isoforms with specific functions. Flies in which the production of tim-shortu0026cold is abrogated display altered patterns of locomotor activity and altered tim expression. Interestingly, the introns of tim carry the information for the temperature sensitivity, suggesting that tim splicing per se is the temperature sensor.