RNA Promotes Synapsin Condensates That Organize Synaptic Vesicles in Live Neurons and Enable Localized Translation in Reconstituted System
Condensates at synapses organize synaptic vesicle (SV) clusters and are essential for efficient neurotransmitter release. While it is established that RNA granules traffic along axons, the function of RNA at the presynapse remains unclear. Here, we uncover a direct structural role of coding RNAs in organizing presynaptic condensates by focusing on SV clusters, condensates between synapsin-1 and lipid vesicles. Using in vitro reconstitution systems, we show that RNA drives synapsin-1 coacervation, with structured RNAs being more effective at promoting phase transitions. The importance of RNA was confirmed in living synapses, where acute disruption of native RNA induces a dispersion of SVs and synapsin. Conversely, ectopically expressed SV-like condensates contained the translational machinery. The microscopy-based in vitro translation assay demonstrates increased translation efficiency within synapsin-1/RNA condensates. Together, our work indicates a novel structural role of RNAs in modulating SV condensates.
Authors
- Marina Jendrach (ORCID: https://orcid.org/0000-0002-8601-2277)
- Amy S. Gladfelter (ORCID: https://orcid.org/0000-0002-2490-6945)
- Geert van den Bogaart (ORCID: https://orcid.org/0000-0003-2180-6735)
- Dragomir Milovanović (ORCID: https://orcid.org/0000-0002-6625-1879)
- Kiara Freitag (ORCID: https://orcid.org/0000-0002-5244-3140)
- Branislava Ranković (ORCID: https://orcid.org/0000-0001-8642-9809)
- Sofiia Reshetniak (ORCID: https://orcid.org/0000-0003-4847-4144)
- Stephan J. Sigrist (ORCID: https://orcid.org/0000-0002-1698-5815)
- Christian Hoffmann (ORCID: https://orcid.org/0000-0003-3478-2410)
- Ian Seim (ORCID: https://orcid.org/0000-0001-9719-2552)
- Michaela Müller-McNicoll (ORCID: https://orcid.org/0000-0002-7174-8310)
- Vladimir Jovanović (ORCID: https://orcid.org/0000-0002-8056-5065)
- Rinse de Boer (ORCID: https://orcid.org/0000-0002-5350-2683)
- Zachary M. Geisterfer (ORCID: https://orcid.org/0000-0001-5883-6036)
- Akshita Chhabra (ORCID: https://orcid.org/0000-0002-7323-4989)
- Katja Nowick (ORCID: https://orcid.org/0000-0003-3993-4479)
- Frank L. Heppner (ORCID: https://orcid.org/0000-0001-9816-8917)
- Lars T. Hofstede (ORCID: https://orcid.org/0009-0006-1138-0151)
- Gerard Aguilar Pérez
- Antonela Condric
- Vladimir Despic
- Jingao Sun (ORCID: https://orcid.org/0009-0004-5395-1499)
Institutions
- Goethe University Frankfurt (DE)
- Marine Biological Laboratory (US)
- University of Groningen (NL)
- Duke University (US)
- Frankfurt Institute for Advanced Studies (DE)
- Humboldt-Universität zu Berlin (DE)
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE)
- Max Planck Institute of Molecular Cell Biology and Genetics (DE)
- University of Göttingen (DE)
- Freie Universität Berlin (DE)
Publication Details
- Journal
- Advanced Science
- Published
- 2026-08-21
- DOI
- https://doi.org/10.1002/advs.77115
- Primary Topic
- RNA regulation and disease
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Deutsche Forschungsgemeinschaft
- National Institutes of Health
- Air Force Office of Scientific Research