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

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.

• Publication year

  2025

• Venue

  bioRxiv

• Publication date

  2025-11-07

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1101/2025.11.06.686960PMID 41279795PMCID 12637423
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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