TRAP-Seq uncovers post-transcriptional gene regulation after acute sleep deprivation

Sleep deprivation is a rising global health resulting in decrements in learning and performance as well as increasing the incidence and risk of numerous diseases. Sleep deprivation induces significant changes in gene expression in many brain regions as seen through transcriptome studies, with the hippocampus particularly susceptible to sleep deprivation. However, less is known about the effects of sleep deprivation on gene regulation post-transcriptionally. To identify the effects of sleep deprivation on the translatome, we took advantage of the RiboTag mouse line with an HA labeled ribosomal protein to express labeled Rpl22 in CaMKIIalpha neurons to selectively isolate and then sequence mRNA transcripts associated with ribosomes. We found 198 differentially expressed genes in the ribosome bound mRNA subset after sleep deprivation; a much smaller number of affected genes than expected based on previous transcriptome studies suggesting that sleep deprivation affects gene regulation through post-transcriptional mechanisms. In comparison with a previously published data reporting the effects of sleep deprivation on gene expression in the hippocampus, we found that the subset of genes affected by sleep was considerably different at the level of the ribosome compared with the whole transcriptome, with only 49 genes regulated similarly. Interestingly, we found that 478 genes differentially regulated by sleep deprivation in the whole transcriptome were not significantly regulated in the translatome. Conversely there were 149 genes differentially regulated by sleep deprivation in the translatome but not differentially expressed in the whole transcriptome. These results indicate that sleep deprivation targets post-transcriptional mechanisms in gene regulation to affect the pool of actively translated mRNAs.