IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-43535-1.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-43535-1
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-43535-1?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. 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.
    2. Adekunle T. Bademosi & Elsa Lauwers & Pranesh Padmanabhan & Lorenzo Odierna & Ye Jin Chai & Andreas Papadopulos & Geoffrey J. Goodhill & Patrik Verstreken & Bruno van Swinderen & Frédéric A Meunier, 2017. "Erratum: In vivo single-molecule imaging of syntaxin1A reveals polyphosphoinositide- and activity-dependent trapping in presynaptic nanoclusters," Nature Communications, Nature, vol. 8(1), pages 1-1, April.
    3. 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. "Publisher Correction: Nuclear compartmentalization of TERT mRNA and TUG1 lncRNA is driven by intron retention," Nature Communications, Nature, vol. 12(1), pages 1-1, December.
    4. Tristan P. Wallis & Anmin Jiang & Kyle Young & Huiyi Hou & Kye Kudo & Alex J. McCann & Nela Durisic & Merja Joensuu & Dietmar Oelz & Hien Nguyen & Rachel S. Gormal & Frédéric A. Meunier, 2023. "Super-resolved trajectory-derived nanoclustering analysis using spatiotemporal indexing," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    5. Binyamin D. Berkovits & Christine Mayr, 2015. "Alternative 3′ UTRs act as scaffolds to regulate membrane protein localization," Nature, Nature, vol. 522(7556), pages 363-367, June.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Shanley F. Longfield & Rachel S. Gormal & Matis Feller & Pierre Parutto & Jürgen Reingruber & Tristan P. Wallis & Merja Joensuu & George J. Augustine & Ramón Martínez-Mármol & David Holcman & Frédéric, 2024. "Synapsin 2a tetramerisation selectively controls the presynaptic nanoscale organisation of reserve synaptic vesicles," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Carter J. Barger & Abigail K. Suwala & Katarzyna M. Soczek & Albert S. Wang & Min Y. Kim & Chibo Hong & Jennifer A. Doudna & Susan M. Chang & Joanna J. Phillips & David A. Solomon & Joseph F. Costello, 2022. "Conserved features of TERT promoter duplications reveal an activation mechanism that mimics hotspot mutations in cancer," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. Miho M. Suzuki & Kenta Iijima & Koichi Ogami & Keiko Shinjo & Yoshiteru Murofushi & Jingqi Xie & Xuebing Wang & Yotaro Kitano & Akira Mamiya & Yuji Kibe & Tatsunori Nishimura & Fumiharu Ohka & Ryuta S, 2023. "TUG1-mediated R-loop resolution at microsatellite loci as a prerequisite for cancer cell proliferation," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    4. Shanley F. Longfield & Mahdie Mollazade & Tristan P. Wallis & Rachel S. Gormal & Merja Joensuu & Jesse R. Wark & Ashley J. Waardenberg & Christopher Small & Mark E. Graham & Frédéric A. Meunier & Ramó, 2023. "Tau forms synaptic nano-biomolecular condensates controlling the dynamic clustering of recycling synaptic vesicles," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    5. Tristan P. Wallis & Anmin Jiang & Kyle Young & Huiyi Hou & Kye Kudo & Alex J. McCann & Nela Durisic & Merja Joensuu & Dietmar Oelz & Hien Nguyen & Rachel S. Gormal & Frédéric A. Meunier, 2023. "Super-resolved trajectory-derived nanoclustering analysis using spatiotemporal indexing," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    6. Anmin Jiang & Kye Kudo & Rachel S. Gormal & Sevannah Ellis & Sikao Guo & Tristan P. Wallis & Shanley F. Longfield & Phillip J. Robinson & Margaret E. Johnson & Merja Joensuu & Frédéric A. Meunier, 2024. "Dynamin1 long- and short-tail isoforms exploit distinct recruitment and spatial patterns to form endocytic nanoclusters," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    7. Ling-Gang Wu & Chung Yu Chan, 2024. "Membrane transformations of fusion and budding," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    8. Steen W. B. Bender & Marcus W. Dreisler & Min Zhang & Jacob Kæstel-Hansen & Nikos S. Hatzakis, 2024. "SEMORE: SEgmentation and MORphological fingErprinting by machine learning automates super-resolution data analysis," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43535-1. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.