Synaptic control of mRNA translation by reversible assembly of XRN1 bodies

LUCHELLI L; THOMAS MG; BOCCACCIO GL

JOURNAL OF CELL SCIENCE

COMPANY OF BIOLOGISTS LTD

Lugar: Cambridge; Año: 2015 vol. 128 p. 1542 - 1554

0021-9533

Repression of mRNA translation is linked to the formation of specific cytosolic foci such as Stress Granules (SGs) and Processing Bodies (PBs), which store or degrade mRNAs. In neurons, synaptic activity regulates translation at the postsynapse and this is important for plasticity. NMDA receptor stimulation downregulates translation and we speculate that this is linked to the formation of unknown mRNA-silencing foci. Here we show that the 5´-3´ exoribonuclease XRN1 forms discrete clusters associated to the postsynapse that are different from PBs or SGs, and we named them Synaptic XRN1-bodies (SX-bodies). Using primary neurons, we found that the SX-bodies respond to synapse stimulation and that their formation correlates inversely with the local translation rate. SX-bodies enlarge in size and number upon NMDA stimulation, and metabotropic glutamate receptor activation provokes SX-body dissolution, along with increased translation. The response is specific and the previously described Smaug1-foci and FMRP granules show a different response. Finally, XRN1 knockdown impairs the translational repression triggered by NMDA. Collectively, these observations support a role for the SX-bodies in the reversible masking and silencing of mRNAs at the synapse