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Related Concept Videos

Circadian Rhythms and Gene Regulation02:19

Circadian Rhythms and Gene Regulation

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The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent...
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Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
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The intricate hormonal interplay essential for male reproductive health begins with the release of gonadotropin-releasing hormone (GnRH) by the hypothalamus. This hormone prompts the pituitary gland to secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH). LH targets the Leydig cells in the testes, stimulating them to produce and release testosterone. In concert with testosterone, FSH acts on the Sertoli cells within the seminiferous tubules to facilitate the release of...
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Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
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In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing...
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Related Experiment Video

Updated: Jan 20, 2026

Monitoring Cell-autonomous Circadian Clock Rhythms of Gene Expression Using Luciferase Bioluminescence Reporters
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The NRON complex controls circadian clock function through regulated PER and CRY nuclear translocation.

Yool Lee1,2, Yang Shen3,4, Lauren J Francey1,5

  • 1Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.

Scientific Reports
|August 17, 2019
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The NRON complex regulates the circadian clock by controlling PER and CRY protein movement into the nucleus. This finding offers new insights into circadian timekeeping and potential therapeutic targets.

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Area of Science:

  • Chronobiology
  • Molecular Cell Biology
  • Signal Transduction

Background:

  • Post-translational modifications are crucial for circadian clock function.
  • Nucleocytoplasmic translocation of core clock proteins is essential for circadian timekeeping but not fully understood.
  • The NRON scaffolding complex was previously shown to regulate NFAT nuclear translocation.

Purpose of the Study:

  • To investigate the role of the NRON complex in the circadian clock mechanism.
  • To determine if NRON components influence the subcellular localization of core clock proteins.
  • To explore the impact of targeting the NFAT pathway on circadian rhythms.

Main Methods:

  • Genetic perturbation of NRON complex components in peripheral cell clock models.
  • Analysis of PER and CRY protein nuclear translocation, amplitude, and period length.
  • Treatment with small molecules targeting the NFAT pathway in peripheral cells and suprachiasmatic nucleus explants.

Main Results:

  • Genetic disruption of the NRON complex altered PER and CRY nuclear translocation, reduced circadian amplitude, and modified period length in peripheral cells.
  • Small molecules targeting the NFAT pathway affected PER and CRY nuclear translocation.
  • Circadian rhythms in peripheral cells and suprachiasmatic nucleus tissue explants were impacted by NFAT pathway modulation.

Conclusions:

  • The NRON complex plays a significant role in regulating the circadian clock.
  • NRON complex components are key regulators of PER/CRY protein subcellular localization.
  • Targeting the NFAT pathway influences circadian timekeeping, suggesting a link between NFAT signaling and circadian rhythms.