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

被引:5
|
作者
Liau, Wei-Siang [1 ]
Zhao, Qiongyi [1 ]
Bademosi, Adekunle [2 ]
Gormal, Rachel S. [2 ]
Gong, Hao [1 ]
Marshall, Paul R. [1 ]
Periyakaruppiah, Ambika [1 ]
Madugalle, Sachithrani U. [1 ]
Zajaczkowski, Esmi L. [1 ]
Leighton, Laura J. [1 ]
Ren, Haobin [1 ]
Musgrove, Mason [1 ]
Davies, Joshua [1 ]
Rauch, Simone [3 ]
He, Chuan [3 ]
Dickinson, Bryan C. [3 ]
Li, Xiang [4 ,5 ]
Wei, Wei [4 ]
Meunier, Frederic A. [2 ,6 ]
Fernandez-Moya, Sandra M. [7 ,11 ,12 ]
Kiebler, Michael A. [7 ]
Srinivasan, Balakumar [8 ]
Banerjee, Sourav [8 ]
Clark, Michael [9 ]
Spitale, Robert C. [10 ]
Bredy, Timothy W. [1 ]
机构
[1] Univ Queensland, Queensland Brain Inst, Cognit Neuroepigenet Lab, Brisbane, Qld, Australia
[2] Univ Queensland, Queensland Brain Inst, Single Mol Neurosci Lab, Brisbane, Qld, Australia
[3] Univ Chicago, Dept Chem, Chicago, IL USA
[4] Wuhan Univ, Zhongnan Hosp, Dept Neurosurg, Wuhan, Peoples R China
[5] Wuhan Univ, Med Res Inst, Wuhan, Peoples R China
[6] Univ Queensland, Sch Biomed Sci, Brisbane, Qld, Australia
[7] Ludwig Maximilian Univ Munich, Biomed Ctr, Munich, Germany
[8] Natl Brain Res Ctr, Manesar, India
[9] Univ Melbourne, Dept Anat & Physiol, Parkville, Vic, Australia
[10] Univ Calif Irvine, Dept Pharmaceut Sci, Irvine, CA USA
[11] Bellvitge Inst Biomed Res IDIBELL, Regenerat Med Program, Gene Regulat Cell Ident, Barcelona 08908, Spain
[12] Program Adv Clin Translat Regenerat Med Catalonia, P CMR C, Barcelona 08908, Spain
基金
澳大利亚国家健康与医学研究理事会;
关键词
PHASE-SEPARATION; TRANSCRIPTOME; MEMORY; EXPRESSION; PLASTICITY; EVOLUTION; STRESS; INTRON; GAS5;
D O I
10.1038/s41467-023-43535-1
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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. Synaptic activity controls the extinction of conditioned fear. Here the authors discovered a new way that the brain controls memories of fear: a long noncoding RNA called Gas5 that coordinates the activity of RNA granules in the synaptic compartment.
引用
收藏
页数:16
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