skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

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

Abstract

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.

Authors:
; ; ; ; ; ; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1492703
Report Number(s):
PNNL-SA-138421
Journal ID: ISSN 2405-4712
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Journal Name:
Cell Systems
Additional Journal Information:
Journal Volume: 7; Journal Issue: 6; Journal ID: ISSN 2405-4712
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
circadian, Neurospora, proteome, Tandem Mass Tag Mass Spectrometry, post-transcriptional regulation, elongation, metabolism, CSP-1

Citation Formats

Hurley, Jennifer M., Jankowski, Meaghan S., De los Santos, Hannah, Crowell, Alexander M., Fordyce, Samuel B., Zucker, Jeremy D., Kumar, Neeraj, Purvine, Samuel O., Robinson, Errol W., Shukla, Anil, Zink, Erika, Cannon, William R., Baker, Scott E., Loros, Jennifer J., and Dunlap, Jay C. Circadian Proteomic Analysis Uncovers Mechanisms of Post-Transcriptional Regulation in Metabolic Pathways. United States: N. p., 2018. Web. doi:10.1016/j.cels.2018.10.014.
Hurley, Jennifer M., Jankowski, Meaghan S., De los Santos, Hannah, Crowell, Alexander M., Fordyce, Samuel B., Zucker, Jeremy D., Kumar, Neeraj, Purvine, Samuel O., Robinson, Errol W., Shukla, Anil, Zink, Erika, Cannon, William R., Baker, Scott E., Loros, Jennifer J., & Dunlap, Jay C. Circadian Proteomic Analysis Uncovers Mechanisms of Post-Transcriptional Regulation in Metabolic Pathways. United States. doi:10.1016/j.cels.2018.10.014.
Hurley, Jennifer M., Jankowski, Meaghan S., De los Santos, Hannah, Crowell, Alexander M., Fordyce, Samuel B., Zucker, Jeremy D., Kumar, Neeraj, Purvine, Samuel O., Robinson, Errol W., Shukla, Anil, Zink, Erika, Cannon, William R., Baker, Scott E., Loros, Jennifer J., and Dunlap, Jay C. Sat . "Circadian Proteomic Analysis Uncovers Mechanisms of Post-Transcriptional Regulation in Metabolic Pathways". United States. doi:10.1016/j.cels.2018.10.014.
@article{osti_1492703,
title = {Circadian Proteomic Analysis Uncovers Mechanisms of Post-Transcriptional Regulation in Metabolic Pathways},
author = {Hurley, Jennifer M. and Jankowski, Meaghan S. and De los Santos, Hannah and Crowell, Alexander M. and Fordyce, Samuel B. and Zucker, Jeremy D. and Kumar, Neeraj and Purvine, Samuel O. and Robinson, Errol W. and Shukla, Anil and Zink, Erika and Cannon, William R. and Baker, Scott E. and Loros, Jennifer J. and Dunlap, Jay C.},
abstractNote = {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.},
doi = {10.1016/j.cels.2018.10.014},
journal = {Cell Systems},
issn = {2405-4712},
number = 6,
volume = 7,
place = {United States},
year = {2018},
month = {12}
}