<i>pumilio</i> regulates sleep homeostasis in response to chronic sleep deprivation in <i>Drosophila melanogaster</i>

Jesús-Olmo, Luis A. De; Rodríguez, Norma; Francia, Marcelo; Alemán-Rios, Jonathan; Pacheco-Agosto, Carlos J.; Ortega-Torres, Joselyn; Nieves, Richard; Fuenzalida‐Uribe, Nicolás; Ghezzi, Alfredo; Agosto, José

doi:10.1101/833822

Cited by 2 publications

(2 citation statements)

References 79 publications

(55 reference statements)

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“…The vinegar fly Drosophila has proved to be a useful model organism for understanding the molecular and cellular mechanisms regulating sleep (15,16). The powerful genetic tools available in the fly, along with the ability to manipulate and measure neural signaling within small groups of defined cell types, have revealed genes and brain networks that mediate the homeostatic regulation of sleep (17)(18)(19)(20). Furthermore, such work in the fly has revealed mechanisms that also mediate sleep regulation in mammals (21,22).…”

Section: Introductionmentioning

confidence: 99%

Homeostatic Control of Deep Sleep inDrosophila: Implications for Discovering Correlates of Sleep Pressure

Chowdhury

Abhilash

Ortega

et al. 2022

Preprint

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A defining feature of sleep is its homeostatic control, which is most clearly expressed as increased sleep after forced wakefulness. Drosophila has served as a powerful model system for understanding the homeostatic control of sleep and ongoing work continues to be an important complement to studies in mammals and other vertebrate models. Nevertheless, there are significant challenges confronting investigators of sleep regulation in Drosophila. For example, the magnitude of sleep rebound in flies is relatively modest, providing a small dynamic range over which to detect changes in homeostatic responses in experimental subjects. In addition, the perturbation necessary to keep flies awake is associated with physiological and behavioral responses that may obscure homeostatic sleep responses. Furthermore, the analysis of fly sleep as a unitary state, without differentiation between shallow and deep sleep states, clouds our ability to fully characterize homeostatic sleep responses. To address these challenges, we describe the development of a yoked-controlled paradigm for flies that allows us to produce two sets of flies that have experienced identical levels of mechanical perturbation while suffering significantly different amounts of sleep deprivation. Moreover, by differentiating long bouts of sleep from all sleep, we show that flies display significant and lasting homeostatic increases in such long bouts following sleep deprivation, that are only detectable when controlling for the sleep-independent effects of mechanical deprivation. Finally, we illustrate the importance of yoked controls for examining the molecular correlates of sleep pressure. Our work introduces methodological approaches that are likely to support the discovery of new mechanisms of sleep regulation in the fly and calls for the reevaluation of previous work identifying the molecular, physiological, and cellular correlates of sleep pressure.

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Section: Introductionmentioning

confidence: 99%

Homeostatic Control of Deep Sleep inDrosophila: Implications for Discovering Correlates of Sleep Pressure

Chowdhury

Abhilash

Ortega

et al. 2022

Preprint

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“…Drosophila Pumilio -the founding member of the PUM family -Is characterized as a translational repressor and is involved in embryo patterning, fertility and the regulation of neuronal homeostasis 31,[37][38][39][40] . PUM proteins act as posttranscriptional regulators, by interacting with consensus sequences called Pumilio regulatory elements (PRE) in the 3'UTRs of target mRNAs 9 to modulate their translation and/or degradation [41][42] .…”

Section: Introductionmentioning

confidence: 99%

Pumilio protects Xbp1 mRNA from regulated Ire1-dependent decay

Cairrão

A³

et al. 2021

Preprint

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The unfolded protein response (UPR) maintains homeostasis of the endoplasmic reticulum (ER). Residing in the ER membrane, the UPR mediator Ire1 deploys its cytoplasmic kinase-endoribonuclease domain to activate the key UPR transcription factor Xbp1 through non-conventional splicing of Xbp1 mRNA. Ire1 also degrades diverse ER-targeted mRNAs through regulated Ire1-dependent decay (RIDD), but how it spares Xbp1 mRNA from this decay is unknown. We identified binding sites for the RNA-binding protein Pumilio in the 3 UTR Drosophila Xbp1. In the developing Drosophila eye, Pumilio bound both the Xbp1unspliced and Xbp1spliced mRNAs, but only Xbp1spliced was stabilized by Pumilio. Furthermore, Pumilio displayed Ire1 kinase-dependent phosphorylation during ER stress, which was required for its stabilization of Xbp1spliced. Human IRE1 could directly phosphorylate Pumilio, and phosphorylated Pumilio protected Xbp1spliced mRNA against RIDD. Thus, Ire1-mediated phosphorylation enables Pumilio to shield Xbp1spliced from RIDD. These results uncover an important and unexpected regulatory link between an RNA-binding protein and the UPR.

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pumilio regulates sleep homeostasis in response to chronic sleep deprivation in Drosophila melanogaster

Cited by 2 publications

References 79 publications

Homeostatic Control of Deep Sleep inDrosophila: Implications for Discovering Correlates of Sleep Pressure

Homeostatic Control of Deep Sleep inDrosophila: Implications for Discovering Correlates of Sleep Pressure

Pumilio protects Xbp1 mRNA from regulated Ire1-dependent decay

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