Circadian rhythms are generated by cyclic transcription, translation, and degradation of clock gene products, including timeless (tim), 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 tim in Drosophila. We found that at 18 °C, TIM levels are low due to the induction of two cold-specific isoforms: tim-cold and tim-short&cold. At 29 °C, another isoform, tim-medium, is upregulated. This isoform switching regulates the levels and activity of TIM as each isoform has a specific function. We found that tim-short&cold encodes a protein that rescues the behavioral defects of tim01 mutants and that flies in which tim-short&cold is abrogated have abnormal locomotor activity. In addition, miRNA-mediated control limits the expression of some of these isoforms. Finally, our data using minigenes suggest that tim alternative splicing might act as a thermometer for the circadian clock.
- Sebastian Kadener
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Mani Ramaswami, Trinity College Dublin, Ireland
- Received: December 21, 2018
- Accepted: November 7, 2019
- Accepted Manuscript published: November 8, 2019 (version 1)
© 2019, Martin Anduaga et al.
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