Abstract
Author SummaryThe circadian clock controls daily rhythms in physiology and behavior via mechanisms that regulate gene expression. While numerous studies have examined the clock regulation of gene transcription and documented rhythms in mRNA abundance, less is known about how circadian changes in protein synthesis contribute to the orchestration of physiological and behavioral programs. Here we have monitored mRNA ribosomal association (as a proxy for translation) to globally examine the circadian timing of protein synthesis specifically within clock cells of Drosophila. The results reveal, for the first time in any organism, the complete circadian program of protein synthesis (the “circadian translatome”) within these cells. A novel finding is that most mRNAs within clock cells are translated at one of two predominant circadian phases—midday or mid-night—times of low energy expenditure. Our work also finds that many clock cell processes, including metabolism, redox state, signaling, neurotransmission, and even protein synthesis itself, are coordinately regulated such that mRNAs required for similar cellular functions are translated in synchrony at the same time of day.
Highlights
Genetic studies carried out in several model systems have provided seminal knowledge about the biochemistry of the circadian molecular oscillator and the neural circuitry regulating circadian behavior
Our results reveal a daily synchronization of protein synthesis and identify novel cycling mRNAs within clock cells that are required for diverse physiological processes
While numerous studies have examined the clock regulation of gene transcription and documented rhythms in mRNA abundance, less is known about how circadian changes in protein synthesis contribute to the orchestration of physiological and behavioral programs
Summary
Genetic studies carried out in several model systems have provided seminal knowledge about the biochemistry of the circadian molecular oscillator and the neural circuitry regulating circadian behavior. In Drosophila and mammals, a well-characterized TTFL oscillator consisting of several canonical clock genes regulates circadian behavioral rhythms (reviewed in [1]). A few studies have documented cell-type–specific transcriptional rhythms [5,6,7], due to methodological limitations. Most of those studies utilized Fluorescence-Activated Cell Sorting (FACS), the manual isolation of identified cells, or cellspecific transcriptional profiling techniques, but such methods are either not applicable to all cell populations or lack the sensitivity to detect the entire transcriptome; nor do they distinguish between ribosome-bound (i.e., translating) and soluble mRNA without the use of polyribosome isolation
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