piRNAs are regulators of metabolic reprogramming in stem cells.

Autor: Rojas-Ríos P; Institute of Human Genetics, Université de Montpellier, CNRS, Montpellier, France.; Departamento de Genética, Facultad de Biología, Universidad de Sevilla, Sevilla, Spain., Chartier A; Institute of Human Genetics, Université de Montpellier, CNRS, Montpellier, France., Enjolras C; Institute of Human Genetics, Université de Montpellier, CNRS, Montpellier, France., Cremaschi J; Institute of Human Genetics, Université de Montpellier, CNRS, Montpellier, France., Garret C; Institute of Human Genetics, Université de Montpellier, CNRS, Montpellier, France., Boughlita A; Institute of Human Genetics, Université de Montpellier, CNRS, Montpellier, France., Ramat A; Institute of Human Genetics, Université de Montpellier, CNRS, Montpellier, France., Simonelig M; Institute of Human Genetics, Université de Montpellier, CNRS, Montpellier, France. Martine.Simonelig@igh.cnrs.fr.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Sep 27; Vol. 15 (1), pp. 8405. Date of Electronic Publication: 2024 Sep 27.
DOI: 10.1038/s41467-024-52709-4
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE