Synaptically recruited lncRNA SLAMR facilitates structural plasticity in fear memory consolidation by modulatin translation
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Orbitrap Fusion ETD
ORGANISM(S): Mus Musculus (ncbitaxon:10090)
SUBMITTER: 
Sathyanarayanan Puthanveettil
PROVIDER: MSV000091477 | MassIVE | Mon Mar 13 09:19:00 GMT 2023
SECONDARY ACCESSION(S): PXD040815
REPOSITORIES: MassIVE
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Project description:Long noncoding RNAs (lncRNAs) represent a multidimensional class of regulatory molecules involved in many aspects of brain function. Emerging evidence indicates that lncRNAs are expressed at the synapse; however, a direct role for their activity in this subcellular compartment in memory formation has yet to be demonstrated. Using lncRNA capture-seq on synaptosomes, we identified a significant number of lncRNAs that accumulate at synapses within the infralimbic prefrontal cortex of adult male C57/Bl6 mice. Among these is a splice variant related to the stress-associated lncRNA, Gas5. RNA immunoprecipitation followed by mass spectrometry and single molecule imaging revealed that this Gas5 isoform, in association with the RNA binding proteins G3bp2 and Caprin1, regulates the activity-dependent trafficking and clustering of RNA granules in dendrites. In addition, we found that cell-type-specific, state-dependent, and synapse-specific knockdown of the Gas5 variant led to impaired fear extinction memory. These findings identify a new mechanism of fear extinction that involves the dynamic interaction between local lncRNA activity and the coordination of RNA condensates in the synaptic compartment.
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