Circadian period is compensated for repressor protein turnover rates in single cells.

Proc Natl Acad Sci U S A

Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Division of Chronobiology, Berlin 10117, Germany.

Published: August 2024

AI Article Synopsis

  • Most mammalian cells possess circadian clocks that regulate the timing of various biological processes, but how they adapt to changes in metabolism is not well understood.* -
  • This study utilized single-cell analysis to explore the relationship between circadian rhythms and protein stability without altering genes, focusing on key proteins involved in the circadian clock.* -
  • Findings revealed that the duration of circadian rhythms adjusts based on the degradation rates of repressor proteins, with stability influenced by the phase of the circadian cycle, challenging existing theories about these mechanisms.*

Article Abstract

Most mammalian cells have molecular circadian clocks that generate widespread rhythms in transcript and protein abundance. While circadian clocks are robust to fluctuations in the cellular environment, little is known about the mechanisms by which the circadian period compensates for fluctuating metabolic states. Here, we exploit the heterogeneity of single cells both in circadian period and a metabolic parameter-protein stability-to study their interdependence without the need for genetic manipulation. We generated cells expressing key circadian proteins (CRYPTOCHROME1/2 (CRY1/2) and PERIOD1/2 (PER1/2)) as endogenous fusions with fluorescent proteins and simultaneously monitored circadian rhythms and degradation in thousands of single cells. We found that the circadian period compensates for fluctuations in the turnover rates of circadian repressor proteins and uncovered possible mechanisms using a mathematical model. In addition, the stabilities of the repressor proteins are circadian phase dependent and correlate with the circadian period in a phase-dependent manner, in contrast to the prevailing model.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348271PMC
http://dx.doi.org/10.1073/pnas.2404738121DOI Listing

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