Translin Is Required for Metabolic Regulation of Sleep

Kazuma Murakami, Maria E. Yurgel, Bethany A. Stahl, Pavel Masek, Aradhana Mehta, Rebecca Heidker, Wesley Bollinger, Robert M. Gingras, Young Joon Kim, William W. Ja, Beat Suter, Justin R. Diangelo, Alex C. Keene

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Dysregulation of sleep or feeding has enormous health consequences. In humans, acute sleep loss is associated with increased appetite and insulin insensitivity, while chronically sleep-deprived individuals are more likely to develop obesity, metabolic syndrome, type II diabetes, and cardiovascular disease. Conversely, metabolic state potently modulates sleep and circadian behavior; yet, the molecular basis for sleep-metabolism interactions remains poorly understood. Here, we describe the identification of translin (trsn), a highly conserved RNA/DNA binding protein, as essential for starvation-induced sleep suppression. Strikingly, trsn does not appear to regulate energy stores, free glucose levels, or feeding behavior suggesting the sleep phenotype of trsn mutant flies is not a consequence of general metabolic dysfunction or blunted response to starvation. While broadly expressed in all neurons, trsn is transcriptionally upregulated in the heads of flies in response to starvation. Spatially restricted rescue or targeted knockdown localizes trsn function to neurons that produce the tachykinin family neuropeptide Leucokinin. Manipulation of neural activity in Leucokinin neurons revealed these neurons to be required for starvation-induced sleep suppression. Taken together, these findings establish trsn as an essential integrator of sleep and metabolic state, with implications for understanding the neural mechanism underlying sleep disruption in response to environmental perturbation.

Original languageEnglish (US)
Pages (from-to)972-980
Number of pages9
JournalCurrent Biology
Volume26
Issue number7
DOIs
StatePublished - Apr 4 2016

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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    Murakami, K., Yurgel, M. E., Stahl, B. A., Masek, P., Mehta, A., Heidker, R., Bollinger, W., Gingras, R. M., Kim, Y. J., Ja, W. W., Suter, B., Diangelo, J. R., & Keene, A. C. (2016). Translin Is Required for Metabolic Regulation of Sleep. Current Biology, 26(7), 972-980. https://doi.org/10.1016/j.cub.2016.02.013