ArticlePLoS biology2025
Upstream open reading frames dynamically modulate CLOCK protein translation to regulate circadian rhythms and sleep.
Article in PLoS biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Circadian synchronization between diet and gut microbiota in modulating host's health.Gut microbes · 2026Review
- Ginsenosides alleviate the progression of hepatic fibrosis by targeting the liver circadian clock geneMolecular medicine reports · 2026Article
- Genome-wide pQTL mapping in human skin identifies specific genetic regulators and mechanistic links to skin disorders.Nature communications · 2026Article
- The birth, death, and evolutionary compensation of uORFs in Drosophila.Nucleic acids research · 2026Article
- Predicted bacterial uRBSs reveal translational coupling and ribosome-mediated RBS occlusion as gene-controlling mechanisms.microLife · 2026Article
- Sleep regulation inFrontiers in neuroscience · 2026Review
- Integrating serum pharmacochemistry with network pharmacology and pharmacological validation to elucidate the mechanism of KaiXinSan in treating insomnia.BMC complementary medicine and therapies · 2025Article
- Tissue-specific CLOCK isoforms modulate circadian feedback loops to govern reproductive fitness in Drosophila.Cellular and molecular life sciences : CMLS · 2025Article
- Clock Gene Expression Modulation by Low- and High-Intensity Exercise Regimens in Aging Mice.International journal of molecular sciences · 2025Article
- Dynamic effects of sleep deprivation on emotional behavior, circadian rhythm genes, and inflammatory infiltration in the medial prefrontal cortex.Frontiers in behavioral neuroscience · 2025Article
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Authors and funding
8 authors.
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Abstract
The circadian rhythm is an evolutionarily conserved mechanism with translational regulation increasingly recognized as pivotal in its modulation. In this study, we found that upstream open reading frames (uORFs) are enriched in Drosophila circadian rhythm genes, with particularly conserved uORFs present in core circadian clock genes. We demonstrate evidence that the uORFs of the core clock gene, Clock (Clk), rhythmically and substantially attenuate CLK protein translation in Drosophila, with pronounced suppression occurring during daylight hours. Eliminating Clk uORFs leads to increased CLK protein levels during the day and results in a shortened circadian cycle, along with a broad shift in clock gene expression rhythms. Notably, Clk uORF deletion also augments morning sleep by reducing dopaminergic activity. Beyond daily circadian adjustments, Clk uORFs play a role in modulating sleep patterns in response to seasonal daylight variations. Furthermore, the Clk uORFs act as an important regulator to shape the rhythmic expression of a vast array of genes and influence multifaceted physiological outcomes. Collectively, our research sheds light on the intricate ways uORFs dynamically adjust downstream coding sequences to acclimate to environmental shifts.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.