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Peer-reviewedCC BY 4.0Advanced Science

RNA Promotes Synapsin Condensates That Organize Synaptic Vesicles in Live Neurons and Enable Localized Translation in Reconstituted System

10 more authors
11 affiliations
  1. 1Whitman Center Marine Biological Laboratory Woods Hole Massachusetts USA
  2. 2Institute of Biochemistry Charité‐Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin Humboldt‐Universität Berlin and Berlin Institute of Health & Laboratory of Molecular Neuroscience German Center for Neurodegenerative Diseases (DZNE) Berlin Germany
  3. 3Institute of Biology Freie Universität Berlin Berlin Germany
  4. 4Department of Cell Biology Duke University Durham North Carolina USA
  5. 5Human Biology and Primate Evolution Freie Universität Berlin Berlin Germany
  6. 6Max Planck Institute for Molecular Cell Biology and Genetics Dresden Germany
  7. 7Department of Molecular Immunology Groningen Biomolecular Sciences and Biotechnology Institute University of Groningen Groningen The Netherlands
  8. 8Department of Neuropathology Charité ‐ Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin Humboldt‐Universität Zu Berlin and Berlin Institute of Health & German Center for Neurodegenerative Diseases (DZNE) Berlin Germany
  9. 9Goethe University Frankfurt Institute For Molecular Biosciences Frankfurt am Main Germany
  10. 10Institute For Neuro‐ and Sensory Physiology University Medical Center Göttingen Göttingen Germany
  11. 11Einstein Center for Neuroscience Charité‐Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin Humboldt‐Universität Berlin and Berlin Institute of Health Berlin Germany

Abstract

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.

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BibTeX
@article{rankovic2026promotes,
  title = {{RNA Promotes Synapsin Condensates That Organize Synaptic Vesicles in Live Neurons and Enable Localized Translation in Reconstituted System}},
  author = {Branislava Rankovic and Zachary M. Geisterfer and Akshita Chhabra and Vladimir M. Jovanovic and Ian Seim and Christian Hoffmann and Antonela Condric and Gerard Aguilar Pérez and Rinse de Boer and Lars T. Hofstede and Jingao Sun and Kiara Freitag and Katja Nowick and Marina Jendrach and Frank L. Heppner and Vladimir Despic and Michaela Müller‐McNicoll and Stephan Sigrist and Geert van den Bogaart and Sofiia Reshetniak and Amy S. Gladfelter and Dragomir Milovanovic},
  journal = {Advanced Science},
  year = {2026},
  month = aug,
  doi = {10.1002/advs.77115},
  url = {https://doi.org/10.1002/advs.77115},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - RNA Promotes Synapsin Condensates That Organize Synaptic Vesicles in Live Neurons and Enable Localized Translation in Reconstituted System
AU  - Branislava Rankovic
AU  - Zachary M. Geisterfer
AU  - Akshita Chhabra
AU  - Vladimir M. Jovanovic
AU  - Ian Seim
AU  - Christian Hoffmann
AU  - Antonela Condric
AU  - Gerard Aguilar Pérez
AU  - Rinse de Boer
AU  - Lars T. Hofstede
AU  - Jingao Sun
AU  - Kiara Freitag
AU  - Katja Nowick
AU  - Marina Jendrach
AU  - Frank L. Heppner
AU  - Vladimir Despic
AU  - Michaela Müller‐McNicoll
AU  - Stephan Sigrist
AU  - Geert van den Bogaart
AU  - Sofiia Reshetniak
AU  - Amy S. Gladfelter
AU  - Dragomir Milovanovic
PY  - 2026
DA  - 2026/08/21
JO  - Advanced Science
DO  - 10.1002/advs.77115
UR  - https://doi.org/10.1002/advs.77115
AB  - 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.
SN  - 2198-3844
ER  -