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      A Clockwork Wikipedia: From a Broad Perspective to a Case Study

      1 , 2
      Journal of Biological Rhythms
      SAGE Publications

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          Internet encyclopaedias go head to head.

          Jim Giles (2005)
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            Circadian Clocks in Human Red Blood Cells

            Summary Circadian (~24 hour) clocks are fundamentally important for coordinated physiology in organisms as diverse as cyanobacteria and humans. All current models of the clockwork in eukaryotic cells are based on transcription-translation feedback loops. Non-transcriptional mechanisms in the clockwork have been difficult to study in mammalian systems. We circumvented these problems by developing novel assays using human red blood cells (RBCs), which have no nucleus (or DNA), and therefore cannot perform transcription. Our results show that transcription is, in fact, not required for circadian oscillations in humans, and that non-transcriptional events appear sufficient to sustain cellular circadian rhythms. Using RBCs, we found that peroxiredoxins, highly conserved antioxidant proteins, undergo ~24 hour redox cycles, which persist for many days under constant conditions (i.e. in the absence of external cues). Moreover, these rhythms are entrainable (i.e. tunable by environmental stimuli), and temperature-compensated, both key features of circadian rhythms. We anticipate our findings will facilitate more sophisticated cellular clock models, highlighting the interdependency of transcriptional and non-transcriptional oscillations in potentially all eukaryotic cells.
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              Circadian rhythms persist without transcription in a eukaryote

              Circadian rhythms are ubiquitous in eukaryotes, and co-ordinate numerous aspects of behaviour, physiology and metabolism, from sleep/wake cycles in mammals to growth and photosynthesis in plants1,2. This daily timekeeping is thought to be driven by transcriptional/translational feedback loops, whereby rhythmic expression of clock gene products regulates expression of associated genes in approximately 24-hour cycles. The specific transcriptional components differ between phylogenetic kingdoms3. The unicellular pico-eukaryotic alga, Ostreococcus tauri, possesses a naturally minimised clock, which includes many features that are shared with higher eukaryotes (plants), such as a central negative feedback loop that involves the morning-expressed CCA1 and evening-expressed TOC1 genes4. Given that recent observations in animals and plants have revealed prominent post-translational contributions to timekeeping5, 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, though 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 mammals6. Moreover we show that pharmacological modulators of the mammalian clockwork have the same effects on rhythms in Ostreococcus. Post-translational mechanisms, and at least one rhythmic marker, appear to be better conserved than transcriptional clock regulators. It is plausible that the oldest oscillator components are non-transcriptional in nature, as in cyanobacteria7, and are conserved across kingdoms.
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                Author and article information

                Journal
                Journal of Biological Rhythms
                J Biol Rhythms
                SAGE Publications
                0748-7304
                1552-4531
                May 15 2018
                June 2018
                April 17 2018
                June 2018
                : 33
                : 3
                : 233-244
                Affiliations
                [1 ]Cohn Institute for the History and Philosophy of Science and Ideas, Tel Aviv University, Tel Aviv, Israel
                [2 ]Weizmann Institute of Science, Rehovot, Israel
                Article
                10.1177/0748730418768120
                d229d713-5cdb-4cb7-89c9-781514374b93
                © 2018

                http://journals.sagepub.com/page/policies/text-and-data-mining-license


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