Circadian Clocks in Human Red Blood Cells

By J. O’Neill, A. B. Reddy. Nature, 2011

810 citations recorded by the source corpus.

Circadian (∼24 hour) clocks are fundamentally important for coordinated physiology in organisms as diverse as cyanobacteria and humans. All current models of the molecular circadian 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, which have no nucleus (or DNA) and therefore cannot perform transcription. Our results show that transcription is not required for circadian oscillations in humans, and that non-transcriptional events seem to be sufficient to sustain cellular circadian rhythms. Using red blood cells, we found that peroxiredoxins, highly conserved antioxidant proteins, undergo ∼24-hour redox cycles, which persist for many days under constant conditions (that is, in the absence of external cues). Moreover, these rhythms are entrainable (that is, tunable by environmental stimuli) and temperature-compensated, both key features of circadian rhythms. We anticipate that our findings will facilitate more sophisticated cellular clock models, highlighting the interdependency of transcriptional and non-transcriptional oscillations in potentially all eukaryotic cells.

Subfields: Aging, Endocrine and Autonomic Systems, Physiology

View Paper: https://www.semanticscholar.org/paper/3f279af34de6614513b979e9a51a0b25a52b89a6

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Aging

1. J. Takahashi
2. T. Y. Tsai
3. J. Denu
4. Qiong Yang
5. Navdeep S. Chandel
6. J. Ferrell

In Endocrine and Autonomic Systems

1. J. Takahashi
2. J. Bass
3. Ethan D. Buhr
4. T. Y. Tsai
5. Qiong Yang
6. J. Ferrell
7. Satchidananda Panda
8. C. Green

In Physiology

1. Navdeep S. Chandel
2. Christopher B. Newgard
3. J. Bass
4. T. Y. Tsai
5. B. Dickinson
6. Christopher J. Chang
7. J. Takahashi
8. Ethan D. Buhr

Citations in the corpus

• The two‐process model of sleep regulation: a reappraisal (2016, background): “Gene transcription is not a prerequisite for circadian rhythms, and non-transcriptional events are sufficient to sustain circadian rhythms in human red blood cells (O’Neill and Reddy, 2011).”
• Molecular components of the Mammalian circadian clock. (2013, background): “cycles fulfilling other necessary attributes of true circadian clocks (Nakajima et al. 2005; O’Neill and Reddy 2011; Tomita et al. 2005).”
• Circadian Clock NAD+ Cycle Drives Mitochondrial Oxidative Metabolism in Mice (2013, background): “Clocks also receive reciprocal input frommetabolic signals, and metabolic cycles persist with 24-hour rhythmicity even in the absence of transcription (37).”
• Chemistry and biology of reactive oxygen species in signaling or stress responses (2011, background): “Red blood cells, which lack a nucleus and most other organelles, including mitochondria, use 24-h redox cycles of peroxiredoxin proteins that persist for many days, under constant conditions that are entrainable and temperature compensate”
• Modeling the cell cycle: why do certain circuits oscillate? (2011, positive): “, 2011), and human red blood cells (O’Neill and Reddy, 2011), circadian oscillations can proceed in the absence of transcription.”
• Minimal tool set for a prokaryotic circadian clock (2016, background): “However, findings on 17 post-translational systems are accumulating [16, 17, 18] and might exist also in Archaea [16].”