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bioRxiv · 10.1101/2025.11.06.686960

Regulation of miR-219 and its target RalGPS dictates acute synaptic plasticity at the Drosophila neuromuscular junction

Aavula, K.·Heggeness, H.·Yokokura, T.·Van Vactor, D.
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Abstract

RNA regulatory mechanisms mediate adaptive responses requiring rapid gene expression changes. Examining microRNA (miRNA)-mediated control of structural synaptic plasticity, we identified miR-219 and six other conserved miRNAs regulating activity-induced morphogenesis at Drosophila glutamatergic synapses. Among miRNA targets downregulated by acute stimulation, the Ral-activating factor RalGPS is necessary for presynaptic morphogenesis and sufficient to block plasticity. Stimulation elevates miR-219 loading into Argonaute complexes without altering mature miR-219 levels, revealing a post-transcriptional regulatory mechanism. We conclude that activity-induced miRNA loading modulates Ral signaling via RalGPS to enable presynaptic remodeling and growth, establishing a novel link between neuronal activity and synaptic structural plasticity.

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Aavula, K., Heggeness, H., Yokokura, T., Van Vactor, D.. 2025-11-07. Regulation of miR-219 and its target RalGPS dictates acute synaptic plasticity at the Drosophila neuromuscular junction. https://doi.org/10.1101/2025.11.06.686960

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