title: Circadian clock-dependent and -independent rhythmic proteomes implement distinct diurnal functions in mouse liver.
abstract: Diurnal oscillations of gene expression controlled by the circadian clock underlie rhythmic physiology across most living organisms. Although such rhythms have been extensively studied at the level of transcription and mRNA accumulation, little is known about the accumulation patterns of proteins. Here, we quantified temporal profiles in the murine hepatic proteome under physiological light-dark conditions using stable isotope labeling by amino acids quantitative MS. Our analysis identified over 5,000 proteins, of which several hundred showed robust diurnal oscillations with peak phases enriched in the morning and during the night and related to core hepatic physiological functions. Combined mathematical modeling of temporal protein and mRNA profiles indicated that proteins accumulate with reduced amplitudes and significant delays, consistent with protein half-life data. Moreover, a group comprising about one-half of the rhythmic proteins showed no corresponding rhythmic mRNAs, indicating significant translational or posttranslational diurnal control. Such rhythms were highly enriched in secreted proteins accumulating tightly during the night. Also, these rhythms persisted in clock-deficient animals subjected to rhythmic feeding, suggesting that food-related entrainment signals influence rhythms in circulating plasma factors.
authors.affiliation: Department of Pharmacology and Toxicology, University of Lausanne, CH-1005 Lausanne, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Mauvoisin
authors.forename: Jingkui
authors.initials: J
authors.lastname: Wang
authors.forename: Céline
authors.initials: C
authors.lastname: Jouffe
authors.forename: Eva
authors.initials: E
authors.lastname: Martin
authors.forename: Florian
authors.initials: F
authors.lastname: Atger
authors.forename: Patrice
authors.initials: P
authors.lastname: Waridel
authors.forename: Manfredo
authors.initials: M
authors.lastname: Quadroni
authors.forename: Frédéric
authors.initials: F
authors.lastname: Gachon
authors.forename: Felix
authors.initials: F
authors.lastname: Naef
mesh_terms: D000418:Albumins / Q000378:metabolism; D000818:Animals; D057906:Circadian Clocks; D002940:Circadian Rhythm; D056931:Cryptochromes / Q000235:genetics; D005786:Gene Expression Regulation; D008099:Liver / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008962:Models, Theoretical; D010949:Plasma / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D020543:Proteome; D012333:RNA, Messenger / Q000378:metabolism; D000515:alpha 1-Antitrypsin / Q000378:metabolism
chemical_list: D000418:Albumins; C538964:Cry1 protein, mouse; C538967:Cry2 protein, mouse; D056931:Cryptochromes; D020543:Proteome; D012333:RNA, Messenger; D000515:alpha 1-Antitrypsin
keywords: circadian rhythm; liver metabolism; posttranslational regulation; protein secretion; proteomics