The most in-depth proteome study of its kind shows rhythmic RNA is not essential for metabolic proteins to follow a 24-hour rhythm.
Many organisms respond to a rhythm dictated by the circadian clock, a 24-hour light/dark cycle caused by the daily rotation of the Earth. Within cells, daily changes in the levels of a type of RNA called messenger RNA (mRNA) lead to rhythms in the production of specific proteins; these proteins allow an organism to anticipate regular changes in their external environment. But in contrast to expectations, a team of scientists has discovered that the levels of production of many proteins changed despite steady levels of corresponding mRNA. Importantly, the timing of the production of these proteins leads to the coordination of different metabolic pathways that are vital for a cell's overall function.
At the molecular level, the circadian clock allows an organism to anticipate environmental changes and behave accordingly. Just as the resulting rhythms dictate our sleep and wake cycles, the clock regulates metabolism and development in fungi and other biofuel-producing organisms. A better understanding of the effect of the circadian clock on cellular and organismal functions could improve robustness and resilience of plants to light and heat stress.
A team of scientists from Rensselaer Polytechnic Institute, the Geisel School of Medicine at Dartmouth, the Pacific Northwest National Laboratory, and EMSL, the Environmental Molecular Sciences Laboratory, a U.S. Department of Energy Office of Science user facility, determined the protein levels within fungal cells with a circadian clock very similar to the one in humans. They used an advanced mass spectrometer at EMSL to quantify protein levels in the fungus every two hours over a forty-eight-hour period, generating a more comprehensive set of data on protein types and levels than any previous circadian study. Their work confirmed the importance of the circadian clock in regulating the metabolic output of an organism. However, they also noted that the clock in many cases regulated the timing of proteins that carry out metabolic functions independently of mRNA changes. This study highlighted the importance of the production of proteins that is independent of circadian timing. This research significantly advances the understanding of the circadian mechanism and its impact on metabolism.
Biological and Environmental Research Program Manager
Department of Energy, Office of Science
Rensselaer Polytechnic Institute
This work was supported by the U.S. Department of Energy’s Office of Science, Office of Biological and Environmental Research, including support of the Environmental Molecular Sciences Laboratory (EMSL), a DOE Office of Science User Facility; the National Institutes of Health; and Rensselaer Polytechnic Institute startup funds.
Hurley, J., M. Jankowski, H. De Los Santos, A. Crowell, S. Fordyce, J. Zucker, N. Kumar, S. Purvine, E. Robinson, A. Shukla, E. Zink, W. Cannon, S. Baker, J. Loros, and J. Dunlap. “Circadian proteomic analysis uncovers mechanisms of post-transcriptional regulation in metabolic pathways.” Cell Systems 7(6), 613-626.e5 (2018). [DOI: 10.1016/j.cels.2018.10.014]
Paper: Circadian Proteomic Analysis Uncovers Mechanisms of Post-Transcriptional Regulation in Metabolic Pathways
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