title: Clk post-transcriptional control denoises circadian transcription both temporally and spatially.
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.
authors.affiliation: Biological Chemistry Department, Silberman Institute of Life Sciences, Edmund J. Safra Campus, The Hebrew University, Jerusalem 91904, Israel.
authors.forename: Immanuel
authors.initials: I
authors.lastname: Lerner
authors.affiliation: Biological Chemistry Department, Silberman Institute of Life Sciences, Edmund J. Safra Campus, The Hebrew University, Jerusalem 91904, Israel.
authors.forename: Osnat
authors.initials: O
authors.lastname: Bartok
authors.affiliation: Biological Chemistry Department, Silberman Institute of Life Sciences, Edmund J. Safra Campus, The Hebrew University, Jerusalem 91904, Israel.
authors.forename: Victoria
authors.initials: V
authors.lastname: Wolfson
authors.affiliation: Howard Hughes Medical Institute, Biology Department, Brandeis University, 415 South Street, Waltham, Massachusetts 02451, USA.
authors.forename: Jerome S
authors.initials: JS
authors.lastname: Menet
authors.affiliation: Biological Chemistry Department, Silberman Institute of Life Sciences, Edmund J. Safra Campus, The Hebrew University, Jerusalem 91904, Israel.
authors.forename: Uri
authors.initials: U
authors.lastname: Weissbein
authors.affiliation: Biological Chemistry Department, Silberman Institute of Life Sciences, Edmund J. Safra Campus, The Hebrew University, Jerusalem 91904, Israel.
authors.forename: Shaked
authors.identifier: http://orcid.org/0000-0002-0287-1550
authors.initials: S
authors.lastname: Afik
authors.affiliation: Biological Chemistry Department, Silberman Institute of Life Sciences, Edmund J. Safra Campus, The Hebrew University, Jerusalem 91904, Israel.|School of Computer Sciences, Edmund J. Safra Campus, The Hebrew University, Jerusalem 91904, Israel.
authors.forename: Daniel
authors.initials: D
authors.lastname: Haimovich
authors.affiliation: Biological Chemistry Department, Silberman Institute of Life Sciences, Edmund J. Safra Campus, The Hebrew University, Jerusalem 91904, Israel.
authors.forename: Chen
authors.initials: C
authors.lastname: Gafni
authors.affiliation: Biological Chemistry Department, Silberman Institute of Life Sciences, Edmund J. Safra Campus, The Hebrew University, Jerusalem 91904, Israel.|School of Computer Sciences, Edmund J. Safra Campus, The Hebrew University, Jerusalem 91904, Israel.
authors.forename: Nir
authors.initials: N
authors.lastname: Friedman
authors.affiliation: Howard Hughes Medical Institute, Biology Department, Brandeis University, 415 South Street, Waltham, Massachusetts 02451, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Rosbash
authors.affiliation: Biological Chemistry Department, Silberman Institute of Life Sciences, Edmund J. Safra Campus, The Hebrew University, Jerusalem 91904, Israel.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kadener
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D060565:Argonaute Proteins / Q000378:metabolism; D001522:Behavior, Animal; D001665:Binding Sites; D001683:Biological Clocks / Q000235:genetics; D001921:Brain / Q000378:metabolism; D056926:CLOCK Proteins / Q000235:genetics / Q000378:metabolism*; D002940:Circadian Rhythm / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000502:physiology*; D025461:Feedback, Physiological; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D035683:MicroRNAs / Q000378:metabolism; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D013269:Stochastic Processes; D013997:Time Factors; D014158:Transcription, Genetic
chemical_list: D020413:3' Untranslated Regions; C489654:AGO1 protein, Drosophila; D060565:Argonaute Proteins; C120526:Clk protein, Drosophila; D029721:Drosophila Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; C471146:bantam microRNA, Drosophila; D056926:CLOCK Proteins