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Translational changes induced by acute sleep deprivation uncovered by TRAP-Seq
Lisa C Lyons1,2, Snehajyoti Chatterjee3, Yann Vanrobaeys3
1Department of Neuroscience and Pharmacology, Iowa Neuroscience Institute, Carver College of Medicine, University of Iowa, Iowa City, IA, USA. lyons@bio.fsu.edu.
Molecular Brain
|December 4, 2020
Summary
Sleep deprivation alters actively translated genes in the brain, impacting neuronal function. This study reveals significant differences between changes in the transcriptome and translatome following sleep loss.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Sleep deprivation is a prevalent global health issue with detrimental effects on cognitive functions and overall health.
- While transcriptional changes in the brain due to sleep deprivation are documented, the impact on post-transcriptional gene regulation, specifically the translatome, remains less understood.
- The hippocampus is particularly vulnerable to acute sleep deprivation, suggesting region-specific effects on gene regulation.
Purpose of the Study:
- To investigate the effects of sleep deprivation on the translatome in excitatory neurons.
- To compare changes in actively translated mRNAs (translatome) with overall gene expression (transcriptome) in the hippocampus after sleep deprivation.
Main Methods:
- Utilized the RiboTag mouse model to specifically isolate and sequence ribosome-associated mRNAs from CaMKIIα-expressing excitatory neurons.
- Expressed HA-labeled Rpl22 in these neurons to tag actively translated transcripts.
- Analyzed differentially expressed genes in the translatome post-sleep deprivation and compared them with existing transcriptome data.
Main Results:
- Identified 198 differentially expressed genes in the translatome of excitatory neurons following sleep deprivation.
- Found significant divergence between translatome and transcriptome changes, with only 49 genes showing similar regulation.
- Observed 478 genes differentially regulated in the transcriptome but not the translatome, and 149 genes regulated in the translatome but not the transcriptome.
- Pathway analysis indicated distinct biological functions for genes uniquely regulated in either the transcriptome or translatome.
Conclusions:
- Sleep deprivation significantly alters the pool of actively translated mRNAs in excitatory neurons.
- Post-transcriptional regulation plays a crucial role in the brain's response to sleep loss, with distinct functional pathways affected.
- Understanding translatome changes provides a more nuanced view of sleep deprivation's molecular impact on neuronal function.
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