<i>Drosophila</i> PSI controls circadian period and the phase of circadian behavior under temperature cycle via <i>tim</i> splicing.

Abstract

The <i>Drosophila</i> 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 <i>timeless</i> (<i>tim</i>), promoting splicing events favored at warm temperature over those increased at cold temperature. <i>Psi</i> 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 <i>Drosophila</i> circadian rhythms and circadian behavior phase during temperature cycling through its modulation of the <i>tim</i> splicing pattern.