ArticleProceedings of the National Academy of Sciences of the United States of America2023
Mammalian circadian clock proteins form dynamic interacting microbodies distinct from phase separation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 17 citations in OpenAlex.
- Advances in monitoring mammalian circadian components and their rhythms using reporter systems.RSC chemical biology · 2026Review
- Nuclear CK1δ as a critical determinant of PER:CRY complex dynamics and circadian period.eLife · 2026Article
- Core clock protein subcellular dynamics coordinate local and global circadian control in syncytia.The Journal of cell biology · 2026Article
- BMAL1 regulates circadian rhythms via phase separation-mediated transcriptional hub formation.Signal transduction and targeted therapy · 2026Article
- Oligomerization of PER2 as a dynamic mode of regulation of the mammalian circadian clock.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Hsp70s regulate circadian rhythm by interacting with PERIOD.Cell communication and signaling : CCS · 2026Article
- Chemical biology approaches to study and target circadian clocks and their components.FEBS letters · 2026Review
- Nuclear effects play an important role in determining codon usage-dependent human gene expression.Nature communications · 2025Article
- Sequestration of clock proteins into repressive nuclear condensates orchestrates circadian gene repression.bioRxiv : the preprint server for biology · 2025Article
- Core Clock Protein Subcellular Dynamics Coordinate Local and Global Circadian Control in Syncytia.bioRxiv : the preprint server for biology · 2025Article
- Reporter-Mediated Evaluation of the Circadian Oscillations ofClocks & sleep · 2025Article
- CRYing for balance: a repressor lingers through peak circadian transcription.The EMBO journal · 2025Article
- PERspectives on circadian cell biology.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- Circadian Effects of Melatonin Receptor-Targeting Molecules In Vitro.International journal of molecular sciences · 2024Article
- Article
- Regulation of circadian rhythms by clock protein nuclear bodies.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Liquid-liquid phase separation (LLPS) underlies diverse biological processes. Because most LLPS studies were performed in vitro using recombinant proteins or in cells that overexpress protein, the physiological relevance of LLPS for endogenous protein is often unclear. PERIOD, the intrinsically disordered domain-rich proteins, are central mammalian circadian clock components and interact with other clock proteins in the core circadian negative feedback loop. Different core clock proteins were previously shown to form large complexes. Circadian clock studies often rely on experiments that overexpress clock proteins. Here, we show that when Per2 transgene was stably expressed in cells, PER2 protein formed nuclear phosphorylation-dependent slow-moving LLPS condensates that recruited other clock proteins. Super-resolution microscopy of endogenous PER2, however, revealed formation of circadian-controlled, rapidly diffusing nuclear microbodies that were resistant to protein concentration changes, hexanediol treatment, and loss of phosphorylation, indicating that they are distinct from the LLPS condensates caused by protein overexpression. Surprisingly, only a small fraction of endogenous PER2 microbodies transiently interact with endogenous BMAL1 and CRY1, a conclusion that was confirmed in cells and in mice tissues, suggesting an enzyme-like mechanism in the circadian negative feedback process. Together, these results demonstrate that the dynamic interactions of core clock proteins are a key feature of mammalian circadian clock mechanism and the importance of examining endogenous proteins in LLPS and circadian clock studies.
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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.