Translational changes induced by acute sleep deprivation uncovered by TRAP-Seq
- PDF / 5,486,614 Bytes
- 18 Pages / 595.276 x 790.866 pts Page_size
- 30 Downloads / 178 Views
Open Access
RESEARCH
Translational changes induced by acute sleep deprivation uncovered by TRAP‑Seq Lisa C. Lyons1,2* , Snehajyoti Chatterjee1, Yann Vanrobaeys1, Marie E. Gaine1,3 and Ted Abel1
Abstract Sleep deprivation is a global health problem adversely affecting health as well as causing decrements in learning and performance. Sleep deprivation induces significant changes in gene transcription in many brain regions, with the hippocampus particularly susceptible to acute sleep deprivation. However, less is known about the impacts of sleep deprivation on post-transcriptional gene regulation. To identify the effects of sleep deprivation on the translatome, we took advantage of the RiboTag mouse line to express HA-labeled Rpl22 in CaMKIIα neurons to selectively isolate and sequence mRNA transcripts associated with ribosomes in excitatory neurons. We found 198 differentially expressed genes in the ribosome-associated mRNA subset after sleep deprivation. In comparison with previously published data on gene expression in the hippocampus after sleep deprivation, we found that the subset of genes affected by sleep deprivation was considerably different in the translatome compared with the transcriptome, with only 49 genes regulated similarly. Interestingly, we found 478 genes differentially regulated by sleep deprivation in the transcriptome that were not significantly regulated in the translatome of excitatory neurons. Conversely, there were 149 genes differentially regulated by sleep deprivation in the translatome but not in the whole transcriptome. Pathway analysis revealed differences in the biological functions of genes exclusively regulated in the transcriptome or translatome, with protein deacetylase activity and small GTPase binding regulated in the transcriptome and unfolded protein binding, kinase inhibitor activity, neurotransmitter receptors and circadian rhythms regulated in the translatome. These results indicate that sleep deprivation induces significant changes affecting the pool of actively translated mRNAs. Keywords: Sleep deprivation, Ribosome, Memory, Hippocampus, TRAP, RNA, Gene expression Introduction Sleep deprivation is a widespread problem affecting more than one-third of U.S. adults and 70% of teenagers (Center for Disease Control and Prevention, 2017) leading to significant impairments in memory and performance. The effects of sleep deprivation on learning and memory are phylogenetically conserved from invertebrates such as Aplysia and Drosophila to humans [1–5]. Sleep disorders have been linked to neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease, seemingly increasing disease risk and *Correspondence: [email protected] 1 Department of Neuroscience and Pharmacology, Iowa Neuroscience Institute, Carver College of Medicine, University of Iowa, Iowa City, IA, USA Full list of author information is available at the end of the article
progression (reviewed in [6]; [7–9]). The hippocampus appears particularly susceptible to the effects of acute sleep deprivation
Data Loading...
