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

Autor: Liau WS; Cognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia. w.liau@uq.edu.au., Zhao Q; Cognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia., Bademosi A; Single Molecule Neuroscience Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia., Gormal RS; Single Molecule Neuroscience Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia., Gong H; Cognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia., Marshall PR; Cognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia., Periyakaruppiah A; Cognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia., Madugalle SU; Cognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia., Zajaczkowski EL; Cognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia., Leighton LJ; Cognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia., Ren H; Cognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia., Musgrove M; Cognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia., Davies J; Cognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia., Rauch S; Department of Chemistry, The University of Chicago, Chicago, IL, USA., He C; Department of Chemistry, The University of Chicago, Chicago, IL, USA., Dickinson BC; Department of Chemistry, The University of Chicago, Chicago, IL, USA., Li X; Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China.; Medical Research Institute, Wuhan University, Wuhan, China., Wei W; Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China., Meunier FA; Single Molecule Neuroscience Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.; School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, Australia., Fernández-Moya SM; Biomedical Centre, Ludwig Maximilian University of Munich, Munich, Germany.; 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, 08908, Barcelona, Spain., Kiebler MA; Biomedical Centre, Ludwig Maximilian University of Munich, Munich, Germany., Srinivasan B; National Brain Research Centre, Manesar, India., Banerjee S; National Brain Research Centre, Manesar, India., Clark M; Department of Anatomy and Physiology, University of Melbourne, Parkville, VIC, Australia., Spitale RC; Department of Pharmaceutical Sciences, The University of California, Irvine, CA, USA., Bredy TW; Cognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia. t.bredy@uq.edu.au.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Nov 22; Vol. 14 (1), pp. 7616. Date of Electronic Publication: 2023 Nov 22.
DOI: 10.1038/s41467-023-43535-1
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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