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Science. 2019 Oct 11;366(6462). pii: eaav2642. doi: 10.1126/science.aav2642.

The forebrain synaptic transcriptome is organized by clocks but its proteome is driven by sleep.

Author information

1
Institute of Pharmacology and Toxicology, University of Zürich, Zurich, Switzerland.
2
Institute of Medical Psychology, Medical Faculty, LMU Munich, Germany.
3
Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.
4
Functional Genomics Center Zurich, University of Zurich-Eidgenosissche Technische Hochschule, Zurich, Switzerland.
5
Clinical Proteomics Group, Proteomics Program, Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark.
6
Institute of Pharmacology and Toxicology, University of Zürich, Zurich, Switzerland. steven.brown@pharma.uzh.ch charo.robles@med.uni-muenchen.de tyagarajan@pharma.uzh.ch.
7
Institute of Medical Psychology, Medical Faculty, LMU Munich, Germany. steven.brown@pharma.uzh.ch charo.robles@med.uni-muenchen.de tyagarajan@pharma.uzh.ch.

Abstract

Neurons have adapted mechanisms to traffic RNA and protein into distant dendritic and axonal arbors. Taking a biochemical approach, we reveal that forebrain synaptic transcript accumulation shows overwhelmingly daily rhythms, with two-thirds of synaptic transcripts showing time-of-day-dependent abundance independent of oscillations in the soma. These transcripts formed two sharp temporal and functional clusters, with transcripts preceding dawn related to metabolism and translation and those anticipating dusk related to synaptic transmission. Characterization of the synaptic proteome around the clock demonstrates the functional relevance of temporal gating for synaptic processes and energy homeostasis. Unexpectedly, sleep deprivation completely abolished proteome but not transcript oscillations. Altogether, the emerging picture is one of a circadian anticipation of messenger RNA needs in the synapse followed by translation as demanded by sleep-wake cycles.

PMID:
31601739
DOI:
10.1126/science.aav2642

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