Aubergine and piRNAs are key regulators of energy metabolism for stem cell self-renewal

Abstract: Stem cell populations in mammals are preferentially sustained by a high rate in glycolysis instead of oxidative phosphorylation (Oxphos). A similar phenomenon, known as the Warburg effect, is observed in cancer cells to support their fast growth. However, the molecular mechanisms of metabolic reprogramming are poorly understood. The PIWI protein Aubergine (Aub) and PIWI-interacting RNAs (piRNAs) are key regulators of transposable elements and mRNAs in the germline and somatic cells including stem cells. Here, we reveal that Aub and piRNAs activates glycolysis in the Germline Stem Cells (GSCs) of the Drosophila female. High glycolysis is required for GSC self-renewal. Aub loaded with piRNAs binds several glycolytic mRNAs for their activation in GSCs. The loss-of-function of aub promotes a switch in energy metabolism in the GSCs inducing their differentiation. Using FRET metabolic sensors in GSCs, we found an essential role of Aub in maintaining high glycolytic rates in GSCs. Finally, genetic studies support that glycolytic mRNA regulation by Aub is essential for GSC self-renewal. This study demonstrates the role of Aub/piRNAs as key regulators of the metabolic reprogramming in stem cell biology.