Neuronal exosomes transport a miRNA/RISC cargo to preserve germline stem cell integrity during energy stress

During periods of nutrient scarcity, many animals undergo germline quiescence to preserve reproductive capacity, and neurons are often necessary for this adaptation. We show here that starvation causes the release of neuronal miRNA/Argonaute-loaded exosomes following AMPK-regulated trafficking changes within serotonergic neurons. This neuron-to-germ line communication is independent of classical serotonergic neurotransmission, but instead relies on endosome-derived vesicles that carry a pro-quiescent miRNA cargo to modify germline gene expression. Using a miRNA activity sensor, we show that neuronally-expressed miRNAs can extinguish the expression of germline-mRNA targets in an exosome-dependent manner. Our findings demonstrate how an adaptive neuronal response can change gene expression at a distance by re-directing intracellular trafficking to release neuronal exosomes with specific miRNA cargos capable of tracking to their appropriate destinations. One Sentence SummaryNeurons release miRNA Argonaute-containing exosomes to establish germline stem cell quiescence in response to energy stress.