Department of Neurobiology, University of Massachusetts Medical School, Worcester, United States.
Hebrew University of Jerusalem, Jerusalem, Israel.
Elife. 2019 Nov 8;8:e50063. doi: 10.7554/eLife.50063.
The circadian pacemaker consists of transcriptional feedback loops subjected to post-transcriptional and post-translational regulation. While post-translational regulatory mechanisms have been studied in detail, much less is known about circadian post-transcriptional control. Thus, we targeted 364 RNA binding and RNA associated proteins with RNA interference. Among the 43 hits we identified was the alternative splicing regulator P-element somatic inhibitor (PSI). PSI regulates the thermosensitive alternative splicing of (), promoting splicing events favored at warm temperature over those increased at cold temperature. downregulation shortens the period of circadian rhythms and advances the phase of circadian behavior under temperature cycle. Interestingly, both phenotypes were suppressed in flies that could produce TIM proteins only from a transgene that cannot form the thermosensitive splicing isoforms. Therefore, we conclude that PSI regulates the period of circadian rhythms and circadian behavior phase during temperature cycling through its modulation of the splicing pattern.
生物钟的节律器由转录反馈环组成,这些反馈环受到转录后和翻译后调控。虽然已经详细研究了翻译后调节机制,但关于生物钟的转录后控制知之甚少。因此,我们使用 RNA 干扰靶向了 364 种 RNA 结合蛋白和 RNA 相关蛋白。在我们鉴定的 43 个命中靶点中,有一个是可变剪接调节剂 P 元素体节抑制物(PSI)。PSI 调节()的热敏性可变剪接,促进在温暖温度下有利的剪接事件,而不是在寒冷温度下增加的剪接事件。下调会缩短生物钟节律的周期,并在温度循环下提前生物钟行为的相位。有趣的是,在只能从不能形成热敏性剪接异构体的转基因中产生 TIM 蛋白的果蝇中,这两种表型都被抑制。因此,我们得出结论,PSI 通过调节 剪接模式来调节 生物钟节律的周期和温度循环过程中的生物钟行为相位。