title: The proteomic landscape of the suprachiasmatic nucleus clock reveals large-scale coordination of key biological processes.
abstract: The suprachiasmatic nucleus (SCN) acts as the central clock to coordinate circadian oscillations in mammalian behavior, physiology and gene expression. Despite our knowledge of the circadian transcriptome of the SCN, how it impacts genome-wide protein expression is not well understood. Here, we interrogated the murine SCN proteome across the circadian cycle using SILAC-based quantitative mass spectrometry. Of the 2112 proteins that were accurately quantified, 20% (421 proteins) displayed a time-of-day-dependent expression profile. Within this time-of-day proteome, 11% (48 proteins) were further defined as circadian based on a sinusoidal expression pattern with a ∼24 h period. Nine circadianly expressed proteins exhibited 24 h rhythms at the transcript level, with an average time lag that exceeded 8 h. A substantial proportion of the time-of-day proteome exhibited abrupt fluctuations at the anticipated light-to-dark and dark-to-light transitions, and was enriched for proteins involved in several key biological pathways, most notably, mitochondrial oxidative phosphorylation. Additionally, predicted targets of miR-133ab were enriched in specific hierarchical clusters and were inversely correlated with miR133ab expression in the SCN. These insights into the proteomic landscape of the SCN will facilitate a more integrative understanding of cellular control within the SCN clock.
authors.affiliation: Ottawa Institute of Systems Biology and Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Cheng-Kang
authors.initials: CK
authors.lastname: Chiang
authors.affiliation: Department of Biology, University of Toronto Mississauga, Mississauga, Ontario, Canada.
authors.forename: Neel
authors.initials: N
authors.lastname: Mehta
authors.affiliation: Department of Biology, University of Toronto Mississauga, Mississauga, Ontario, Canada.
authors.forename: Abhilasha
authors.initials: A
authors.lastname: Patel
authors.affiliation: Department of Biology, University of Toronto Mississauga, Mississauga, Ontario, Canada.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Ottawa Institute of Systems Biology and Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Ning
authors.affiliation: Ottawa Institute of Systems Biology and Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Janice
authors.initials: J
authors.lastname: Mayne
authors.affiliation: Ottawa Institute of Systems Biology and Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Warren Y L
authors.initials: WY
authors.lastname: Sun
authors.affiliation: Department of Biology, University of Toronto Mississauga, Mississauga, Ontario, Canada.
authors.forename: Hai-Ying M
authors.initials: HY
authors.lastname: Cheng
authors.affiliation: Ottawa Institute of Systems Biology and Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Figeys
mesh_terms: D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D005786:Gene Expression Regulation; D008027:Light; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D010085:Oxidative Phosphorylation; D060066:Protein Interaction Maps; D020543:Proteome / Q000032:analysis / Q000378:metabolism*; D040901:Proteomics / Q000295:instrumentation / Q000379:methods; D013493:Suprachiasmatic Nucleus / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D035683:MicroRNAs; D024101:Mitochondrial Proteins; D020543:Proteome