MicroRNAs Regulate Sleep and Sleep Homeostasis in Drosophila

To discover microRNAs that regulate sleep, we performed a genetic screen using a library of miRNA sponge-expressing flies. We identified 25 miRNAs that regulate baseline sleep; 17 were sleep-promoting and 8 promoted wake. We identified one miRNA that is required for recovery sleep after deprivation...

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Bibliographic Details
Published in:Cell reports (Cambridge) 2018-06, Vol.23 (13), p.3776-3786
Main Authors: Goodwin, Patricia R., Meng, Alice, Moore, Jessie, Hobin, Michael, Fulga, Tudor A., Van Vactor, David, Griffith, Leslie C.
Format: Article
Language:English
Subjects:
Animals
Circadian Rhythm - genetics
Drosophila - genetics
Drosophila - metabolism
let-7
MicroRNAs - antagonists & inhibitors
MicroRNAs - metabolism
Neurons - metabolism
Sleep - genetics
sleep homeostasis
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Summary:To discover microRNAs that regulate sleep, we performed a genetic screen using a library of miRNA sponge-expressing flies. We identified 25 miRNAs that regulate baseline sleep; 17 were sleep-promoting and 8 promoted wake. We identified one miRNA that is required for recovery sleep after deprivation and 8 miRNAs that limit the extent of recovery sleep. 65% of the hits belong to human-conserved families. Interestingly, the majority (75%), but not all, of the baseline sleep-regulating miRNAs are required in neurons. Sponges that target miRNAs in the same family, including the miR-92a/92b/310 family and the miR-263a/263b family, have similar effects. Finally, mutation of one of the screen’s strongest hits, let-7, using CRISPR/Cas-9, phenocopies sponge-mediated let-7 inhibition. Cell-type-specific and temporally restricted let-7 sponge expression experiments suggest that let-7 is required in the mushroom body both during development and in adulthood. This screen sets the stage for understanding the role of miRNAs in sleep. [Display omitted] •A genetic screen identifies sleep-regulating microRNAs in Drosophila•microRNAs regulate amount, structure and homeostatic regulation of sleep•Let-7 regulates sleep through developmental and adult-specific pathways To examine the role of microRNAs in sleep, Goodwin et al. screened a Drosophila microRNA sponge library, identifying 25 microRNAs that regulate sleep. The majority of these were from families well conserved in vertebrates. Let-7, a strong hit from the screen, has both adult and developmental roles.
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2018.05.078