Environmental circadian disruption re-writes liver circadian proteomes

Nat Commun. 2024 Jul 1;15(1):5537. doi: 10.1038/s41467-024-49852-3.

Abstract

Circadian gene expression is fundamental to the establishment and functions of the circadian clock, a cell-autonomous and evolutionary-conserved timing system. Yet, how it is affected by environmental-circadian disruption (ECD) such as shiftwork and jetlag are ill-defined. Here, we provided a comprehensive and comparative description of male liver circadian gene expression, encompassing transcriptomes, whole-cell proteomes and nuclear proteomes, under normal and after ECD conditions. Under both conditions, post-translation, rather than transcription, is the dominant contributor to circadian functional outputs. After ECD, post-transcriptional and post-translational processes are the major contributors to whole-cell or nuclear circadian proteome, respectively. Furthermore, ECD re-writes the rhythmicity of 64% transcriptome, 98% whole-cell proteome and 95% nuclear proteome. The re-writing, which is associated with changes of circadian regulatory cis-elements, RNA-processing and protein localization, diminishes circadian regulation of fat and carbohydrate metabolism and persists after one week of ECD-recovery.

MeSH terms

  • Animals
  • Circadian Clocks* / genetics
  • Circadian Clocks* / physiology
  • Circadian Rhythm* / genetics
  • Circadian Rhythm* / physiology
  • Gene Expression Regulation
  • Jet Lag Syndrome / metabolism
  • Liver* / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Proteome* / metabolism
  • Shift Work Schedule
  • Transcriptome

Substances

  • Proteome