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

Author

Listed:
  • Wei-Siang Liau

    (The University of Queensland)

  • Qiongyi Zhao

    (The University of Queensland)

  • Adekunle Bademosi

    (The University of Queensland)

  • Rachel S. Gormal

    (The University of Queensland)

  • Hao Gong

    (The University of Queensland)

  • Paul R. Marshall

    (The University of Queensland)

  • Ambika Periyakaruppiah

    (The University of Queensland)

  • Sachithrani U. Madugalle

    (The University of Queensland)

  • Esmi L. Zajaczkowski

    (The University of Queensland)

  • Laura J. Leighton

    (The University of Queensland)

  • Haobin Ren

    (The University of Queensland)

  • Mason Musgrove

    (The University of Queensland)

  • Joshua Davies

    (The University of Queensland)

  • Simone Rauch

    (The University of Chicago)

  • Chuan He

    (The University of Chicago)

  • Bryan C. Dickinson

    (The University of Chicago)

  • Xiang Li

    (Zhongnan Hospital of Wuhan University
    Wuhan University)

  • Wei Wei

    (Zhongnan Hospital of Wuhan University)

  • Frédéric A. Meunier

    (The University of Queensland
    The University of Queensland)

  • Sandra M. Fernández-Moya

    (Biomedical Centre, Ludwig Maximilian University of Munich
    Gene Regulation of Cell Identity, Regenerative Medicine Program, Bellvitge Institute for Biomedical Research (IDIBELL) and Program for Advancing Clinical Translation of Regenerative Medicine of Catalonia, P-CMR[C], L’Hospitalet del Llobregat)

  • Michael A. Kiebler

    (Biomedical Centre, Ludwig Maximilian University of Munich)

  • Balakumar Srinivasan

    (National Brain Research Centre)

  • Sourav Banerjee

    (National Brain Research Centre)

  • Michael Clark

    (University of Melbourne)

  • Robert C. Spitale

    (The University of California)

  • Timothy W. Bredy

    (The University of Queensland)

Abstract

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.

Suggested Citation

  • Wei-Siang Liau & Qiongyi Zhao & Adekunle Bademosi & Rachel S. Gormal & Hao Gong & Paul R. Marshall & Ambika Periyakaruppiah & Sachithrani U. Madugalle & Esmi L. Zajaczkowski & Laura J. Leighton & Haob, 2023. "Fear extinction is regulated by the activity of long noncoding RNAs at the synapse," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43535-1
    DOI: 10.1038/s41467-023-43535-1
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    References listed on IDEAS

    as
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    2. Gabrijela Dumbović & Ulrich Braunschweig & Heera K. Langner & Michael Smallegan & Josep Biayna & Evan P. Hass & Katarzyna Jastrzebska & Benjamin Blencowe & Thomas R. Cech & Marvin H. Caruthers & John , 2021. "Nuclear compartmentalization of TERT mRNA and TUG1 lncRNA is driven by intron retention," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
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