Circadian orchestration of the hepatic proteome
Open accessAbstract
Circadian rhythms are essential to health. Their disruption is associated with metabolic diseases in experimental animals and man. Local metabolic rhythms represent an output of tissue-based circadian clocks. Attempts to define how local metabolism is temporally coordinated have focused on gene expression by defining extensive and divergent "circadian transcriptomes" involving 5%-10% of genes assayed. These analyses are inevitably incomplete, not least because metabolic coordination depends ultimately upon temporal regulation of proteins. We therefore conducted a systematic analysis of a mammalian "circadian proteome." Our analysis revealed that up to 20% of soluble proteins assayed in mouse liver are subject to circadian control. Many of these circadian proteins are novel and cluster into discrete phase groups so that the liver's enzymatic profile contrasts dramatically between day and night. Unexpectedly, almost half of the cycling proteins lack a corresponding cycling transcript, as determined by quantitative PCR, microarray, or both and revealing for the first time the extent of posttranscriptional mechanisms as circadian control points. The circadian proteome includes rate-limiting factors in vital pathways, including urea formation and sugar metabolism. These findings provide a new perspective on the extensive contribution of circadian programming to hepatic physiology.
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It has been estimated that 6-20% of the murine proteome exhibits circadian rhythms in tissues such as the SCN and liver.
“Similar to the reported proportion of rhythmic transcripts, it has been estimated that 6-20% of the murine proteome exhibits circadian rhythms in tissues such as the SCN (33,34) and liver (35)(36)(37).”
From Circadian rhythms, metabolism, and chrononutrition in rodents and humans (2016) · cites this paper as [35]
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- Authors
- Reddy, A. B., Karp, N. A., Maywood, E. S., Sage, E. A., Deery, M., O'Neill, J. S., Wong, G. K. Y., Chesham, J., Odell, M., Lilley, K. S., Kyriacou, C. P., & Hastings, M. H.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- University of Cambridge (GB)
- University of Leicester (GB)
- ORCID
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2006-06
- Volume
- 16
- Issue
- 11
- Pages
- 1107-1115
- ISSN
- 0960-9822 (ISSN-L)
- OpenAlex
- W1970657971
- Cited by
- 548
- References
- 32
- Citations by year
- 2026: 10 · 2025: 17 · 2024: 19 · 2023: 13 · 2022: 20 · 2021: 25 · 2020: 26 · 2019: 27 · 2018: 31 · 2017: 29 · 2016: 39 · 2015: 33 · 2014: 38 · 2013: 49 · 2012: 33
- FWCI
- 12.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2603 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- Leicester Research Archive (University of Leicester) (submittedVersion)
- Funders
- Biotechnology and Biological Sciences Research Council (BB/C006941/1)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- circadian rhythm, liver, post-transcriptional regulation, circadian transcriptome, urea cycle, sugar metabolism, metabolic rhythms, circadian clock, mouse liver
- MeSH terms
- Animals, Circadian Rhythm, Gene Expression Regulation, Liver, RNA, Messenger, Urea, Cluster Analysis, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Proteome, Gene Expression Profiling, Proteomics, Carbohydrate Metabolism, Mice
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