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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

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

Bibliographical note

Funding Information:
We thank Paul Hardin and Justin Blau for reagents, and Justin Blau, Rachel Green, Eran Hornstein, Laura Lande-Diner and Daniel Kaganovich for reading the manuscript. S.K. is funded by the European Research Council Starting Grant (ERC #260911) and by the Binational Science Foundation starting grant. O.B. is funded by ICRF. N.F. is funded by the European Research Council (ERC Advanced Investigator Award, #340712). N.F. and S.K. were funded by I-Core 1796/12.

Publisher Copyright:
© 2015 Macmillan Publishers Limited. All rights reserved.

Fingerprint

Dive into the research topics of 'Clk post-transcriptional control denoises circadian transcription both temporally and spatially'. Together they form a unique fingerprint.

Cite this