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Transcriptional feedback oscillators: maybe, maybe not...

Patricia L Lakin-Thomas1

  • 1Department of Biology, York University, Toronto, Ontario, Canada. plakin@yorku.ca

Journal of Biological Rhythms
|April 11, 2006
PubMed
Summary

The standard model of circadian rhythms is challenged by anomalies. New models may involve metabolic feedback loops regulated by clock genes, not just transcription-feedback.

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Area of Science:

  • Chronobiology
  • Molecular Biology
  • Systems Biology

Background:

  • Circadian rhythms are typically modeled as transcription/translation feedback oscillators.
  • This mechanism explains rhythmic clock protein and mRNA levels in various organisms.
  • The standard model has been widely applied across different species.

Purpose of the Study:

  • To review anomalous observations that deviate from the standard transcription/translation feedback model of circadian rhythmicity.
  • To assess the adequacy of the current model in light of accumulating evidence.
  • To propose alternative frameworks for understanding circadian oscillators.

Main Methods:

  • Literature review of molecular data from model organisms (Acetabularia, Synechococcus, Drosophila, Neurospora, mouse).
  • Analysis of studies reporting rhythmicity despite constant transcription of clock genes.
  • Examination of studies involving knockout mutants lacking clock gene function.

Main Results:

  • An increasing number of anomalous observations challenge the standard model.
  • Rhythmicity persists even when clock gene transcription is constant.
  • Circadian rhythms are observed in knockout mutants lacking functional clock genes.

Conclusions:

  • The standard transcription/translation feedback mechanism is insufficient to explain all circadian oscillations.
  • Rhythmic transcription may serve other roles, such as in input/output pathways or enhancing robustness.
  • A revised model may involve non-circadian oscillators (e.g., metabolic feedback loops) gaining circadian properties from regulatory molecules like clock gene products.

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