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

TY - JOUR

T1 - The forebrain synaptic transcriptome is organized by clocks but its proteome is driven by sleep

AU - Noya, Sara B

AU - Colameo, David

AU - Brüning, Franziska

AU - Spinnler, Andrea

AU - Mircsof, Dennis

AU - Opitz, Lennart

AU - Mann, Matthias

AU - Tyagarajan, Shiva K

AU - Robles, Maria S

AU - Brown, Steven A

N1 - Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

PY - 2019/10/11

Y1 - 2019/10/11

N2 - 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.

AB - 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.

U2 - 10.1126/science.aav2642

DO - 10.1126/science.aav2642

M3 - Journal article

C2 - 31601739

SN - 0036-8075

VL - 366

JO - Science (New York, N.Y.)

JF - Science (New York, N.Y.)

IS - 6462

M1 - eaav2642

ER -