Thermosensitive alternative splicing senses and mediates temperature adaptation in Drosophila

Abstract

Circadian rhythms are generated by the cyclic transcription, translation, and degradation of clock gene products, including <i>timeless</i> (<i>tim</i>), but how the circadian clock senses and adapts to temperature changes is not completely understood. Here, we show that temperature dramatically changes the splicing pattern of <i>tim</i> in <i>Drosophila</i>. We found that at 18°C, TIM levels are low because of the induction of two cold-specific isoforms: <i>tim-cold</i> and <i>tim-short and cold</i>. At 29°C, another isoform, <i>tim-medium</i>, is upregulated. Isoform switching regulates the levels and activity of TIM as each isoform has a specific function. We found that <i>tim-short and cold</i> encodes a protein that rescues the behavioral defects of <i>tim⁰¹</i> mutants, and that flies in which <i>tim-short and cold</i> is abrogated have abnormal locomotor activity. In addition, miRNA-mediated control limits the expression of some of these isoforms. Finally, data that we obtained using minigenes suggest that <i>tim</i> alternative splicing might act as a thermometer for the circadian clock.