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

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

Author information

1
Biological Chemistry Department, Silberman Institute of Life Sciences, Edmund J. Safra Campus, The Hebrew University, Jerusalem 91904, Israel.
2
Howard Hughes Medical Institute, Biology Department, Brandeis University, 415 South Street, Waltham, Massachusetts 02451, USA.
3
School of Computer Sciences, Edmund J. Safra Campus, The Hebrew University, Jerusalem 91904, Israel.

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.

PMID:
25952406
PMCID:
PMC4915573
DOI:
10.1038/ncomms8056
[Indexed for MEDLINE]
Free PMC Article

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