piRNAs are regulators of metabolic reprogramming in stem cells

Abstract

AbstractStem 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 inDrosophilagermline stem cells (GSCs). High glycolysis is required for GSC self-renewal andaubloss-of-function induces a metabolic switch in GSCs leading to their differentiation. Aub directly binds glycolytic mRNAs andEnolasemRNA regulation by Aub depends on its 5’UTR. Furthermore, deletion of a piRNA target site inEnolase5’UTR leads to GSC loss. These data reveal an Aub/piRNA function in translational activation of glycolytic mRNAs in GSCs, and pinpoint a new mode of regulation of metabolic reprogramming in stem cells based on small RNAs.