Clk post-transcriptional control denoises circadian transcription both temporally and spatially

Immanuel Lerner, Osnat Bartok, Victoria Wolfson, Jerome S. Menet, Uri Weissbein, Shaked Afik, Daniel Haimovich, Chen Gafni, Nir Friedman, Michael Rosbash, Sebastian Kadener

Research output: Contribution to journalArticlepeer-review

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 without normal 3′ UTR exhibit variable CLK-driven transcription and circadian behaviour as well as ectopic expression of CLK-target genes in the brain. In these flies, the number of the key circadian neurons differs stochastically between individuals and within the two hemispheres of the same brain. Moreover, 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.

Original languageAmerican English
Article number7056
JournalNature Communications
Volume6
DOIs
StatePublished - 8 May 2015

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • General Biochemistry,Genetics and Molecular Biology
  • General Physics and Astronomy

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