Abstract
Circadian rhythms are generated by the 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 because of the induction of two cold-specific isoforms: tim-cold and tim-short and cold. At 29°C, another isoform, tim-medium, is upregulated. Isoform switching regulates the levels and activity of TIM as each isoform has a specific function. We found that tim-short and cold encodes a protein that rescues the behavioral defects of tim01 mutants, and that flies in which tim-short and cold 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 tim alternative splicing might act as a thermometer for the circadian clock.
Highlights
43 Circadian rhythms organize most physiological and behavioral processes to 24 hours cycles (Allada and Chung, 2010; Pilorz et al, 2018)
SUMMARY Circadian rhythms are generated by the cyclic transcription, translation and degradation of clock genes, including timeless
We found that the lower levels of the canonical TIM protein at 18°C are due to the induction 140 of two cold-specific splicing isoforms
Summary
43 Circadian rhythms organize most physiological and behavioral processes to 24 hours cycles (Allada and Chung, 2010; Pilorz et al, 2018). Products of three of these genes, PERIOD (PER), TIMELESS (TIM), and CLOCKWORK ORANGE (CWO) repress CLK-CYC mediated transcription in an oscillatory manner (Hardin and Panda, 2013; Zhou J, 2016) These cycles of transcriptional activation and repression lead to 24-hour molecular oscillations, which generate behavioral rhythms. The per gene of D. yakuba has a 3’-terminal intron, this intron is removed over a wide range of temperatures and photoperiods, consistent with the marginal effect of temperature on this tropical species Despite these findings, it is still not clear how the regulation of the 3’ UTR splicing impacts PER levels or if other transcriptional and/or post-transcriptional events are responsible for the regulation of activity in response to temperature changes
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