piRNAs are regulators of metabolic reprogramming in stem cells

Area of Science:

• * Molecular Biology
• * Stem Cell Biology
• * Metabolism

Background:

• * Stem cells exhibit a metabolic preference for glycolysis over oxidative phosphorylation, influencing their fate.
• * PIWI-interacting RNAs (piRNAs) and PIWI proteins are known to play vital roles in various adult stem cell functions.
• * The precise molecular mechanisms linking stem cell metabolism and small RNA pathways are not fully understood.

Purpose of the Study:

• * To investigate the role of piRNAs and PIWI proteins in regulating stem cell metabolism.
• * To elucidate the molecular mechanisms by which piRNAs and PIWI proteins control glycolysis in Drosophila female germline stem cells (GSCs).
• * To determine if metabolic rewiring mediated by small RNAs influences stem cell self-renewal and differentiation.

Main Methods:

• * Analysis of glycolysis levels in Drosophila GSCs with and without functional PIWI proteins.
• * Examination of mRNA binding by the PIWI protein Aubergine (Aub).
• * Mutation analysis of piRNA target sites within the 5' untranslated region (5'UTR) of glycolytic enzyme mRNAs.

Main Results:

• * piRNAs and the PIWI protein Aubergine (Aub) were found to be essential for activating glycolysis in Drosophila GSCs.
• * Loss of Aub function caused a metabolic shift from glycolysis to oxidative phosphorylation, leading to GSC differentiation.
• * Aub was shown to directly bind glycolytic mRNAs, with regulation of Enolase mRNA dependent on its 5'UTR.
• * Mutations in a piRNA target site within the Enolase 5'UTR resulted in GSC loss.

Conclusions:

• * Aub/piRNA complexes play a critical role in the translational activation of glycolytic mRNAs in GSCs.
• * This study reveals a novel mechanism of metabolic reprogramming in stem cells regulated by small RNAs.
• * The findings highlight the importance of small RNA-mediated translational control in maintaining stem cell pluripotency and function.