RNA promotes synapsin coacervation and modulates local translation

Condensates are found at synapses where they support the clustering of synaptic vesicles (SVs) and neurotransmitter release. The possibility of RNA promoting the formation or function of these condensates is not known. Here, we set out to assess whether RNA affects molecular condensates in the synapse or could be regulated at these sites, focusing on synapsin-1, which is essential for synapse condensates. Using in vitro reconstitution systems, cell lines and neurons, we show that RNA drives synapsin-1 coacervation, with some bias toward structured RNAs being more effective at promoting demixing. 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 have the ability to recruit RNA species and the translational machinery, which accumulates within condensate-microdomains, resulting in increased translation efficacy. Our work indicates a novel role of RNAs in modulating SV condensates, as well as translation, at the synapse.