1. Clk post-transcriptional control denoises circadian transcription both temporally and spatially
- Author
-
Nir Friedman, Daniel Haimovich, Uri Weissbein, Shaked Afik, Michael Rosbash, Chen Gafni, Immanuel Lerner, Osnat Bartok, Victoria Wolfson, Jerome S. Menet, and Sebastian Kadener
- Subjects
Untranslated region ,Time Factors ,Transcription, Genetic ,CLOCK Proteins ,Fluorescent Antibody Technique ,General Physics and Astronomy ,Biology ,Models, Biological ,Article ,General Biochemistry, Genetics and Molecular Biology ,Biological Clocks ,Transcription (biology) ,microRNA ,Animals ,Drosophila Proteins ,RNA, Messenger ,Circadian rhythm ,3' Untranslated Regions ,Transcription factor ,Post-transcriptional regulation ,Sequence Deletion ,Feedback, Physiological ,Neurons ,Genetics ,Regulation of gene expression ,Stochastic Processes ,Binding Sites ,Multidisciplinary ,Behavior, Animal ,fungi ,Brain ,General Chemistry ,Circadian Rhythm ,MicroRNAs ,Drosophila melanogaster ,Gene Expression Regulation ,Argonaute Proteins ,Ectopic expression - Abstract
The transcription factor CLOCK (CLK) is essential for the development and maintenance of circadian rhythms in Drosophila. However, little is known about how CLK levels are controlled. Here, we show that Clk mRNA is strongly regulated post-transcriptionally through its 3’UTR. Flies expressing Clk transgenes missing their normal 3’UTR, exhibited variable CLK-driven transcription and circadian behavior, as well as ectopic expression of CLK-target genes in the brain. Surprisingly, in these flies, the numbers of the key circadian neurons differs stochastically between individuals and within the two hemispheres of the same brain. In addition, flies carrying Clk transgenes with deletions in the binding sites for the miRNA bantam have stochastic number of pacemaker neurons, suggesting that this miRNA mediates the deterministic expression of CLK. Overall our results demonstrate a key role of Clk post-transcriptional control in stabilizing circadian transcription, which is essential for proper development and maintenance of circadian rhythms in Drosophila.
- Published
- 2015