Fear extinction is regulated by long noncoding RNA activity at the synapse
Fear extinction is regulated by long noncoding RNA activity at the synapse
Summary 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.
Bademosi Adekunle、Fernandez Moya Sandra M.、Kiebler Michael A.、Srinivasan Bharath、Banerjee Sourav、Clark Michael、Zhao Qiongyi、Periyakaruppiah Ambika、Madugalle Sachithrani U.、Zajackowski Esmi L.、Ren Haobin、Li Xiang、Wei Wei、Meunier Fr¨|d¨|ric A.、Gormal Rachel、Gong Hao、Leighton Laura J.、Dickinson Bryan C.、Bredy Timothy W.、Spitale Robert C.、Liau Wei-Siang、He Chuan、Musgrove Mason、Rauch Simone、Davies Joshua、Marshall Paul R.
Single Molecule Neuroscience Laboratory, Queensland Brain Institute, The University of QueenslandMunich Centre for Neural Sciences, Ludwig Maximilian University of MunichMunich Centre for Neural Sciences, Ludwig Maximilian University of MunichNational Brain Research CentreNational Brain Research CentreUniversity of MelbourneCognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of QueenslandCognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of QueenslandCognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of QueenslandCognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of QueenslandCognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of QueenslandDepartment of Neurosurgery, Zhongnan Hospital of Wuhan University||Medical Research Institute, Wuhan UniversityDepartment of Neurosurgery, Zhongnan Hospital of Wuhan UniversitySingle Molecule Neuroscience Laboratory, Queensland Brain Institute, The University of Queensland||School of Biomedical Sciences, The University of QueenslandSingle Molecule Neuroscience Laboratory, Queensland Brain Institute, The University of QueenslandCognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of QueenslandCognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of QueenslandDepartment of Chemistry, The University of ChicagoCognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of QueenslandDepartment of Pharmaceutical Sciences, The University of CaliforniaCognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of QueenslandDepartment of Chemistry, The University of ChicagoCognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of QueenslandDepartment of Chemistry, The University of ChicagoCognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of QueenslandCognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of Queensland
基础医学神经病学、精神病学分子生物学
long noncoding RNAsynapseRNA granulessplicingfear extinction memory
Bademosi Adekunle,Fernandez Moya Sandra M.,Kiebler Michael A.,Srinivasan Bharath,Banerjee Sourav,Clark Michael,Zhao Qiongyi,Periyakaruppiah Ambika,Madugalle Sachithrani U.,Zajackowski Esmi L.,Ren Haobin,Li Xiang,Wei Wei,Meunier Fr¨|d¨|ric A.,Gormal Rachel,Gong Hao,Leighton Laura J.,Dickinson Bryan C.,Bredy Timothy W.,Spitale Robert C.,Liau Wei-Siang,He Chuan,Musgrove Mason,Rauch Simone,Davies Joshua,Marshall Paul R..Fear extinction is regulated by long noncoding RNA activity at the synapse[EB/OL].(2025-03-28)[2025-08-08].https://www.biorxiv.org/content/10.1101/2022.03.30.486308.点此复制
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