Biology subjects

Jurczak, E. M.

Publications and source records attributed to Jurczak, E. M..

2 recordsLinked to original sources

bioRxiv2023

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.

developmental biology↗

bioRxiv2023

AMPK regulates small RNA pathway prevalence to mediate soma-to-germ line communication and establish germline stem cell quiescence

It is well established that cells communicate with each other via signaling molecules and pathways. Recent work has further indicated that this transfer of information can breach the soma-to-germ line barrier, thus permitting changes in germline gene expression in response to cellular decisions made in somatic lineages. We show that during periods of extended energy stress AMPK alters small RNA biogenesis in somatic cells, which non-autonomously regulates the quiescence of germline stem cells. By combining both genetic analyses and a novel method of miRNA imaging, we show that AMPK-mediated phosphorylation acts as a molecular switch that drives the re-allocation of the key RNA endonuclease Dicer to the miRNA synthesis pathway during the dauer stage of C. elegans. By modifying Dicer and other components of the miRNA synthesis machinery, AMPK fine-tunes the production of a population of somatic miRNAs that act as a "pro-quiescence" signal to maintain germline integrity during periods of extended energy stress, thus bridging the gap between the soma and the germ line by altering small RNA homeostasis.

molecular biology↗