title: Circadian rhythms persist without transcription in a eukaryote.
abstract: Circadian rhythms are ubiquitous in eukaryotes, and coordinate numerous aspects of behaviour, physiology and metabolism, from sleep/wake cycles in mammals to growth and photosynthesis in plants. This daily timekeeping is thought to be driven by transcriptional-translational feedback loops, whereby rhythmic expression of 'clock' gene products regulates the expression of associated genes in approximately 24-hour cycles. The specific transcriptional components differ between phylogenetic kingdoms. The unicellular pico-eukaryotic alga Ostreococcus tauri possesses a naturally minimized clock, which includes many features that are shared with plants, such as a central negative feedback loop that involves the morning-expressed CCA1 and evening-expressed TOC1 genes. Given that recent observations in animals and plants have revealed prominent post-translational contributions to timekeeping, a reappraisal of the transcriptional contribution to oscillator function is overdue. Here we show that non-transcriptional mechanisms are sufficient to sustain circadian timekeeping in the eukaryotic lineage, although they normally function in conjunction with transcriptional components. We identify oxidation of peroxiredoxin proteins as a transcription-independent rhythmic biomarker, which is also rhythmic in mammals. Moreover we show that pharmacological modulators of the mammalian clock mechanism have the same effects on rhythms in Ostreococcus. Post-translational mechanisms, and at least one rhythmic marker, seem to be better conserved than transcriptional clock regulators. It is plausible that the oldest oscillator components are non-transcriptional in nature, as in cyanobacteria, and are conserved across kingdoms.
authors.affiliation: Centre for Systems Biology at Edinburgh, C.H. Waddington Building, Mayfield Road, Edinburgh EH9 3JD, UK.
authors.forename: John S
authors.initials: JS
authors.lastname: O'Neill
authors.forename: Gerben
authors.initials: G
authors.lastname: van Ooijen
authors.forename: Laura E
authors.initials: LE
authors.lastname: Dixon
authors.forename: Carl
authors.initials: C
authors.lastname: Troein
authors.forename: Florence
authors.initials: F
authors.lastname: Corellou
authors.forename: François-Yves
authors.initials: FY
authors.lastname: Bouget
authors.forename: Akhilesh B
authors.initials: AB
authors.lastname: Reddy
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Millar
mesh_terms: D015415:Biomarkers / Q000032:analysis; D000460:Chlorophyta / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology*; D003513:Cycloheximide / Q000494:pharmacology; D003839:Deoxyadenosines / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D010084:Oxidation-Reduction; D054464:Peroxiredoxins / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D014158:Transcription, Genetic
chemical_list: D015415:Biomarkers; D003839:Deoxyadenosines; D011500:Protein Synthesis Inhibitors; D003513:Cycloheximide; D054464:Peroxiredoxins; C058120:cordycepin