0028 Sleep Duration Influences the Kinetics of Stress Granule Formation

Abstract Introduction Stress granules are non-membrane bound aggregates of messenger ribonucleoproteins that are biomarkers of cellular stress. It has been shown in cells in vitro that suppression of the mammalian target of rapamycin (mTOR) pathway and its non-mammalian orthologue target of rapamycin (TOR) is associated with an increase in stress granule formation. It has also been shown that the mTOR pathway is suppressed in response to sleep deprivation in mice. Despite the possible connection via the TOR/mTOR pathway, there has not been any previous evidence linking sleep deprivation with stress granule formation. Methods Our present investigation uses the nematode Caenorhabditis elegans to model how stress granule formation and clearance are modified by sleep duration. We developed novel strains of C. elegans that model each type of sleep deprivation or enhancement and have RFP-labeled PAB-1 protein, a key component of stress granules. In addition to modifying sleep duration via genetic means, we also sleep deprived wildtype fluorescently labeled animals using mechanical disturbances. Results Animals with enhanced stress-induced sleep have stress granules that are smaller in size and cleared faster than wildtype, while sleep deprived animals have granules that are slower to clear (F11,473 = 7.752, ***p < 0.0001, one-way ANOVA). Animals that were manually deprived of stress-induced sleep were similarly slower to clear stress granules (F5,209 = 5.476 ***p < 0.0001, one-way ANOVA). Interestingly, animals genetically deprived of developmentally-timed sleep does not appear to have more stress granules in the middle of their sleep period than the sleeping wildtype stage (F2,42 = 2.659, p = 0.0729, one-way ANOVA). Conclusion This work demonstrates that the amount of sleep affects stress granule kinetics, which impacts the flow of genetic information inside cells. Support This work was supported by an R15GM122058 (NIH), John P. McNulty scholars program (SJU) and summer scholars program (SJU).