Department of Neuroscience and Pharmacology, Iowa Neuroscience Institute, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
Program in Neuroscience, Department of Biological Science, Florida State University, Tallahassee, FL, USA.
Mol Brain. 2020 Dec 3;13(1):165. doi: 10.1186/s13041-020-00702-5.
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.
睡眠剥夺是一个全球性的健康问题，它不仅对健康产生不利影响，还会导致学习和表现能力下降。睡眠剥夺会引起许多大脑区域的基因转录发生显著变化，而海马体尤其容易受到急性睡眠剥夺的影响。然而，对于睡眠剥夺对转录后基因调控的影响，我们知之甚少。为了确定睡眠剥夺对翻译组的影响，我们利用 RiboTag 小鼠系在 CaMKIIα 神经元中表达 HA 标记的 Rpl22，以选择性地分离和测序与兴奋性神经元核糖体相关的 mRNA 转录本。我们发现，睡眠剥夺后核糖体相关 mRNA 亚群中有 198 个差异表达基因。与之前关于睡眠剥夺后海马体基因表达的研究相比，我们发现，与转录组相比，受睡眠剥夺影响的基因亚群在翻译组中差异很大，仅有 49 个基因的调控方式相似。有趣的是，我们在转录组中发现了 478 个受睡眠剥夺调节但在兴奋性神经元翻译组中未受显著调节的基因。相反，有 149 个基因在翻译组中受睡眠剥夺调节，但在整个转录组中不受调节。通路分析显示，仅在转录组或翻译组中受到调节的基因的生物学功能存在差异，转录组中调节的基因功能有蛋白去乙酰化酶活性和小 GTP 酶结合，翻译组中调节的基因功能有未折叠蛋白结合、激酶抑制剂活性、神经递质受体和昼夜节律。这些结果表明，睡眠剥夺会引起显著的变化，影响活跃翻译的 mRNA 池。
