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Cell Syst. 2018 Dec 26;7(6):613-626.e5. doi: 10.1016/j.cels.2018.10.014. Epub 2018 Dec 12.

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

Author information

1
Department of Biological Sciences, Rensselaer Polytechnic Institute, Troy, NY 12180, USA. Electronic address: hurlej2@rpi.edu.
2
Department of Biological Sciences, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
3
Department of Computer Science, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
4
Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.
5
Biological Sciences Division, Pacific Northwest National Laboratory, 902 Battelle Blvd, Richland, WA 99352, USA; Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, 902 Battelle Blvd, Richland, WA 99352, USA.
6
Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, 902 Battelle Blvd, Richland, WA 99352, USA; Environmental Molecular Sciences Division, Pacific Northwest National Laboratory, 902 Battelle Blvd, Richland, WA 99352, USA.
7
Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.
8
Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA. Electronic address: jay.c.dunlap@dartmouth.edu.

Abstract

Transcriptional and 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 newly developed 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, and our analysis predicts that these protein rhythms arise from oscillations in translational rates. 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. The transcription factor CSP-1 plays a role in this metabolic regulation, contributing to the rhythmicity and phase of clock-regulated proteins.

KEYWORDS:

CSP-1; Neurospora; circadian; metabolism; post-transcriptional regulation; proteome; tandem mass tag mass spectrometry; translational elongation

PMID:
30553726
DOI:
10.1016/j.cels.2018.10.014

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