piRNAs are regulators of metabolic reprogramming in stem cells

Patricia Rojas-Ríos, Aymeric Chartier, Camille Enjolras, Julie Cremaschi, Céline Garret, Adel Boughlita, Anne Ramat and Martine Simonelig ()
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Patricia Rojas-Ríos: Université de Montpellier, CNRS
Aymeric Chartier: Université de Montpellier, CNRS
Camille Enjolras: Université de Montpellier, CNRS
Julie Cremaschi: Université de Montpellier, CNRS
Céline Garret: Université de Montpellier, CNRS
Adel Boughlita: Université de Montpellier, CNRS
Anne Ramat: Université de Montpellier, CNRS
Martine Simonelig: Université de Montpellier, CNRS

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract Stem cells preferentially use glycolysis instead of oxidative phosphorylation and this metabolic rewiring plays an instructive role in their fate; however, the underlying molecular mechanisms remain largely unexplored. PIWI-interacting RNAs (piRNAs) and PIWI proteins have essential functions in a range of adult stem cells across species. Here, we show that piRNAs and the PIWI protein Aubergine (Aub) are instrumental in activating glycolysis in Drosophila female germline stem cells (GSCs). Higher glycolysis is required for GSC self-renewal and aub loss-of-function induces a metabolic switch in GSCs leading to their differentiation. Aub directly binds glycolytic mRNAs and Enolase mRNA regulation by Aub depends on its 5′UTR. Furthermore, mutations of a piRNA target site in Enolase 5′UTR lead to GSC loss. These data reveal an Aub/piRNA function in translational activation of glycolytic mRNAs in GSCs, and pinpoint a mechanism of regulation of metabolic reprogramming in stem cells based on small RNAs.

Date: 2024
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DOI: 10.1038/s41467-024-52709-4

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