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

Nat Commun. 2015 May 8;6:7056. doi: 10.1038/ncomms8056.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Argonaute Proteins / metabolism
  • Behavior, Animal
  • Binding Sites
  • Biological Clocks / genetics
  • Brain / metabolism
  • CLOCK Proteins / genetics
  • CLOCK Proteins / metabolism*
  • Circadian Rhythm / genetics*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / physiology*
  • Feedback, Physiological
  • Fluorescent Antibody Technique
  • Gene Expression Regulation*
  • MicroRNAs / metabolism
  • Models, Biological
  • Neurons / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sequence Deletion
  • Stochastic Processes
  • Time Factors
  • Transcription, Genetic*

Substances

  • 3' Untranslated Regions
  • AGO1 protein, Drosophila
  • Argonaute Proteins
  • Clk protein, Drosophila
  • Drosophila Proteins
  • MicroRNAs
  • RNA, Messenger
  • bantam microRNA, Drosophila
  • CLOCK Proteins