Fear extinction is regulated by the activity of long noncoding RNAs at the synapse

Journal article

Long noncoding RNAs (lncRNAs) represent a multidimensional class of regulatory molecules that are involved in many aspects of brain function. Emerging evidence indicates that lncRNAs are localized to 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, we identified a specific set of lncRNAs that accumulate in the synaptic compartment within the infralimbic prefrontal cortex of adult male C57/Bl6 mice. Among these was 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 addition, we found that cell-type-specific, activity-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 RNA condensates in the synaptic compartment

Authors: Liau, W-S; Zhao, Q; Bademosi, A; Gormal, RS; Gong, H

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Research
• Journal: Nature Communications
• Volume: 14
• Issue: 1
• Pages: 7616-7616
• Article number: 7616
• Publication date: 2023-11-22
• DOI: 10.1038/s41467-023-43535-1
• EISSN: 2041-1723
• ISSN: 2041-1723
• Language: English
• Keywords: Neuroscience; Genetics; Computational biology; Biology; Long non-coding RNA; Paleontology; Gene; Extinction (optical mineralogy); Synapse; RNA