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Circadian Proteomic Analysis Uncovers Mechanisms of Post-Transcriptional Regulation in Metabolic Pathways

Journal Article · · Cell Systems

Transcriptional/translational feedback loops in fungi and animals drive circadian rhythms in transcript levels that provide output from the clock, but post-transcriptional mechanisms also contribute. To determine the extent and underlying source of this regulation, we applied novel analytical tools to a long-duration, deeply-sampled, circadian proteomics time course comprising half of the proteome. We found a quarter of expressed proteins are clock-regulated, but >40% of these do not arise from clock-regulated transcripts. Contrary to predictions, rhythmic protein degradation plays little role in posttranscriptional regulation but instead rhythms arise from oscillations in translation. Our data highlighted the impact of the clock on metabolic regulation, with central carbon metabolism reflecting both transcriptional and post-transcriptional control and opposing metabolic pathways showing peak activities at different times of day. CSP-1, a transcription factor with a role in metabolic regulation of the clock, contributes significantly to determining the rhythmicity and phase of clock-regulated proteins.

Research Organization:
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
Sponsoring Organization:
USDOE
DOE Contract Number:
AC05-76RL01830
OSTI ID:
1492703
Report Number(s):
PNNL-SA-138421
Journal Information:
Cell Systems, Journal Name: Cell Systems Journal Issue: 6 Vol. 7; ISSN 2405-4712
Publisher:
Elsevier
Country of Publication:
United States
Language:
English