MicroRNAs Regulate Sleep and Sleep Homeostasis in Drosophila

Publication date: 26 June 2018
Source:Cell Reports, Volume 23, Issue 13
Author(s): Patricia R. Goodwin, Alice Meng, Jessie Moore, Michael Hobin, Tudor A. Fulga, David Van Vactor, Leslie C. Griffith
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.

Graphical abstract

Teaser

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.


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