Missions : In the context of an ANR project (Aging-jou), the Post-Doctorant will participate to the characterisation of the role of a cluster of 3 snoRNAs, including jouvence, in the determination of longevity, aging, and neurodegeneration, in Drosophila.

Scientific Context : In the last few years, in Drosophila, we have identified a new small nucleolar RNA (snoRNA) (jouvence) and showed that its mutation (deletion) reduces lifespan, while its overexpression increases it. At the organismal level, the old mutant flies show more neurodegenerative lesions than the controls, while the flies overexpressing jouvence show only few lesions, suggesting a neuroprotection. The mutants present also a hypertrophy of the fat body, indicating a perturbation of the lipids metabolism (triglycerides and cholesterol). jouvence is required in the epithelium of the gut (enterocytes) (Soulé et al., Nat. Comm., 2020). Since, the overexpression of jouvence in the gut increases lifespan, it allows us to hypothesize that the brain lesions in old flies might be a consequence of the deregulation of the lipids metabolism, and more particularly of the cholesterol (gut-brain axis) (Soulé et al., bioRxiv, 2020). However, recently, a deeper characterization of this genomic locus has shown the presence of two other snoRNAs, revealing rather a cluster of three snoRNAs. The objectives of this project are to determine the role of each snoRNAs, such as the longevity, the neurodegenerative and intestinal lesions, as well as the metabolic perturbations (gut-brain axis) of each snoRNA mutant. At the molecular level, the study of the molecular mechanisms of the each snoRNA (pseudouridylation/RNA modification, spliceosome, putative role in chromatin structure, etc.), as well as their putative effect on ribogenesis and protein synthesis (proteome) will also be considered.

1) Soulé S, Mellottée L, Arab A, Chen C, Martin JR. (2020). Jouvence a small nucleolar RNA required in the gut extends lifespan in Drosophila. Nature Communication, 11, 987.

2) Soulé and Martin (2020). ninaD regulates cholesterol homeostasis from the midgut, which protects against neurodegeneration (bioRxiv; https://doi.org/10.1101/2020.11.27.401059).