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The Proteomic Landscape of the Suprachiasmatic Nucleus Clock Reveals Large-Scale Coordination of Key Biological Processes


The suprachiasmatic nucleus (SCN) serves as the master circadian pacemaker in mammals, coordinating the physiological responses of a myriad of peripheral clocks throughout the body and linking their rhythms to the environmental light-dark cycle. In this study, we interrogated the murine SCN proteome across the circadian cycle using stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative mass spectrometry. Among 3275 identified proteins in the SCN, 421 displayed a time-of-day-dependent expression profile, 48 fit a circadian expression profile with a ∼24 h period, and a surprising number of proteins were ultradianly expressed. Nine circadianly expressed proteins were accompanied by transcripts that were also 24 h rhythmic, but with a significant time lag (>8 h) between the phases of peak mRNA vs. protein expression. A substantial proportion of the time-of-day proteome exhibited abrupt fluctuations at the anticipated dawn and dusk, and was involved in 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. Our study underscores the significance of post-transcriptional regulation, the surprising prevalence of ultradian protein expression, and the functional implications on mitochondrial energy metabolism.


Vyšlo v časopise: The Proteomic Landscape of the Suprachiasmatic Nucleus Clock Reveals Large-Scale Coordination of Key Biological Processes. PLoS Genet 10(10): e32767. doi:10.1371/journal.pgen.1004695
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004695

Souhrn

The suprachiasmatic nucleus (SCN) serves as the master circadian pacemaker in mammals, coordinating the physiological responses of a myriad of peripheral clocks throughout the body and linking their rhythms to the environmental light-dark cycle. In this study, we interrogated the murine SCN proteome across the circadian cycle using stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative mass spectrometry. Among 3275 identified proteins in the SCN, 421 displayed a time-of-day-dependent expression profile, 48 fit a circadian expression profile with a ∼24 h period, and a surprising number of proteins were ultradianly expressed. Nine circadianly expressed proteins were accompanied by transcripts that were also 24 h rhythmic, but with a significant time lag (>8 h) between the phases of peak mRNA vs. protein expression. A substantial proportion of the time-of-day proteome exhibited abrupt fluctuations at the anticipated dawn and dusk, and was involved in 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. Our study underscores the significance of post-transcriptional regulation, the surprising prevalence of ultradian protein expression, and the functional implications on mitochondrial energy metabolism.


Zdroje

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Genetika Reprodukčná medicína

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PLOS Genetics


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