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J Cell Sci ; 128(8): 1542-54, 2015 Apr 15.
Article in English | MEDLINE | ID: mdl-25736288

ABSTRACT

Repression of mRNA translation is linked to the formation of specific cytosolic foci such as stress granules and processing bodies, which store or degrade mRNAs. In neurons, synaptic activity regulates translation at the post-synapse and this is important for plasticity. N-methyl-D-aspartate (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 with the post-synapse that are different from processing bodies or stress granules, 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 increase 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.


Subject(s)
DNA-Binding Proteins/metabolism , Exoribonucleases/metabolism , RNA, Messenger/genetics , Receptors, Metabotropic Glutamate/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Synapses/metabolism , Amino Acid Sequence , Animals , Cells, Cultured , Gene Expression Regulation , Mice , Molecular Sequence Data , Neurons/metabolism , Organelles , Protein Biosynthesis , Rats, Sprague-Dawley
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