A Novel Pathway for Sensory-Mediated Arousal Involves Splicing of an Intron in the period Clock Gene
A Novel Pathway for Sensory-Mediated Arousal Involves Splicing of an Intron in the period Clock Gene
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DOI：
10.5665/sleep.4322
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发表时间：
2015-01-01
期刊：
影响因子：
5.6
通讯作者：
Edery, Isaac
中科院分区：
文献类型：
--
作者：
Cao, Weihuan;Edery, Isaac
研究目的：D.黑腹鼠是研究昼夜节律（与24小时一致）计时系统和睡眠如何调节每日觉醒-睡眠周期的极好动物模型。来自昼夜节律钟基因period（per）的温度敏感的3 '-末端内含子（称为dmpi 8）的剪接调节果蝇的日常活动的分布。dmpi 8剪接对日常行为的作用进行了进一步评估，通过分析sleep.Design：转基因苍蝇的相同的遗传背景，但表达野生型重组每基因或其中的dmpi 8剪接的效率增加暴露于不同的温度在每天的光-暗周期和睡眠参数测量。此外，转基因苍蝇短暂地暴露于各种感官介导的刺激，以测量唤醒responses.Results：令人惊讶的是，我们表明，dmpi 8剪接对白天活动水平的影响不涉及昼夜节律的作用，但与感官依赖的觉醒和睡眠行为的调整。具有高dmpi 8剪接效率的基因改变的果蝇在用光和非光线索（例如机械刺激）进行短时间处理后保持更长的唤醒时间。我们提出dmpi 8剪接的热调节在一种新的唤醒机制中起着温度校准变阻器的作用，因此在温暖的日子里，dmpi 8内含子的无效剪接通过减少感觉介导的唤醒而触发静止的增加，从而确保苍蝇在炎热的正午阳光下最小化活动，尽管环境中存在光，这通常是昼行动物的强烈唤醒线索。
Study Objectives: D. melanogaster is an excellent animal model to study how the circadian (congruent to 24-h) timing system and sleep regulate daily wake-sleep cycles. Splicing of a temperature-sensitive 3'-terminal intron (termed dmpi8) from the circadian clock gene period (per) regulates the distribution of daily activity in Drosophila. The role of dmpi8 splicing on daily behavior was further evaluated by analyzing sleep.Design: Transgenic flies of the same genetic background but expressing either a wild-type recombinant per gene or one where the efficiency of dmpi8 splicing was increased were exposed to different temperatures in daily light-dark cycles and sleep parameters measured. In addition, transgenic flies were briefly exposed to a variety of sensory-mediated stimuli to measure arousal responses.Results: Surprisingly, we show that the effect of dmpi8 splicing on daytime activity levels does not involve a circadian role for per but is linked to adjustments in sensory-dependent arousal and sleep behavior. Genetically altered flies with high dmpi8 splicing efficiency remain aroused longer following short treatments with light and non-photic cues such as mechanical stimulation.Conclusions: We propose that the thermal regulation of dmpi8 splicing acts as a temperature-calibrated rheostat in a novel arousal mechanism, so that on warm days the inefficient splicing of the dmpi8 intron triggers an increase in quiescence by decreasing sensory-mediated arousal, thus ensuring flies minimize being active during the hot midday sun despite the presence of light in the environment, which is usually a strong arousal cue for diurnal animals.