CONICET | Buscador de Institutos y Recursos Humanos

XRN1 is a RNA binding protein with 5- 3´ exoribonuclease activity present in all cell types. In almost all cases, XRN1 concentrates in discrete foci, termed Processing Bodies (PBs). We found that in neurons, XRN1 doesnt colocalize with PBs, but form discrete structures associated to the postsynapse, that we call NPSAXs (Non PB Synapse-associated XRN1). We found that 40 % of synapses contain NPSAXs. The NPSAXs are dynamic; they increase in number and size when mRNAs are released from polysomes, and dissolve upon treatment with drugs that stabilizes polysomes. Moreover, the NPSAXs respond to distinct synaptic stimuli. NMDAR activation provokes an enhancement in NPSAX, whereas mGluR stimulation provokes their dissolution. In all cases, we found that the stability of the NPSAXs upon synaptic stimulation correlates inversely with polysome integrity. We have previously shown that other synaptic mRNA silencing foci, termed S-foci, as they contain the translational repressor Smaug 1, respond with a distinct pattern. The stimulation of NMDA receptor or mGluR provoke a rapid and reversible disassembly of the S-foci. Likewise NPSAXs, the stability of the S-foci upon synaptic stimulation correlates inversely with polysome stability. Using a recently described strategy termed FUNCAT, which allow monitoring protein synthesis in situ, we found that local translation at the synapse is stimulated by mGluR activity, whereas NMDAR stimulation inhibits local translation. We conclude that the NPSAXs harbour mRNAs that are silenced upon NMDA receptor stimulation, whereas they release mRNA to allow their translation upon metabotropic receptor stimulation. Collectively, these observations highlight the selective use of distinct mRNA silencing foci for the fine tuning of local protein synthesis at the synapse.