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

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 for...

Descripción completa

Detalles Bibliográficos
Autores: Liau, Wei Siang, Zhao, Qiongyi, Bademosi, Adekunle, Gormal, Rachel S., Gong, Hao, Marshall, Paul R., Periyakaruppiah, Ambika, Madugalle, Sachithrani U., Zajaczkowski, Esmi L., Leighton, Laura J., Ren, Haobin, Musgrove, Mason, Davies, Joshua, Rauch, Simone, He, Chuan, Dickinson, Bryan C., Li, Xiang, Wei, Wei, Meunier, Frédéric A., Fernández Moya, Sandra M., Kiebler, Michael A., Srinivasan, Balakumar, Banerjee, Sourav, Clark, Michael, Spitale, Robert C., Bredy, Timothy W.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/206244
Acceso en línea:https://hdl.handle.net/2445/206244
Access Level:acceso abierto
Palabra clave:Escorça frontal
Sinapsi
Prefrontal Cortex
Synapses
id ES_533bf61aaa41966afca47d5b06f9384e
oai_identifier_str oai:diposit.ub.edu:2445/206244
network_acronym_str ES
network_name_str España
repository_id_str
spelling Fear extinction is regulated by the activity of long noncoding RNAs at the synapseLiau, Wei SiangZhao, QiongyiBademosi, AdekunleGormal, Rachel S.Gong, HaoMarshall, Paul R.Periyakaruppiah, AmbikaMadugalle, Sachithrani U.Zajaczkowski, Esmi L.Leighton, Laura J.Ren, HaobinMusgrove, MasonDavies, JoshuaRauch, SimoneHe, ChuanDickinson, Bryan C.Li, XiangWei, WeiMeunier, Frédéric A.Fernández Moya, Sandra M.Kiebler, Michael A.Srinivasan, BalakumarBanerjee, SouravClark, MichaelSpitale, Robert C.Bredy, Timothy W.Escorça frontalSinapsiPrefrontal CortexSynapsesLong 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.Springer Science and Business Media LLC2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/206244Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1038/s41467-023-43535-1Nature Communications, 2023, vol. 14, num. 1https://doi.org/10.1038/s41467-023-43535-1cc by (c) Liau, Wei Siang et al., 2023http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2062442026-05-27T06:46:51Z
dc.title.none.fl_str_mv Fear extinction is regulated by the activity of long noncoding RNAs at the synapse
title Fear extinction is regulated by the activity of long noncoding RNAs at the synapse
spellingShingle Fear extinction is regulated by the activity of long noncoding RNAs at the synapse
Liau, Wei Siang
Escorça frontal
Sinapsi
Prefrontal Cortex
Synapses
title_short Fear extinction is regulated by the activity of long noncoding RNAs at the synapse
title_full Fear extinction is regulated by the activity of long noncoding RNAs at the synapse
title_fullStr Fear extinction is regulated by the activity of long noncoding RNAs at the synapse
title_full_unstemmed Fear extinction is regulated by the activity of long noncoding RNAs at the synapse
title_sort Fear extinction is regulated by the activity of long noncoding RNAs at the synapse
dc.creator.none.fl_str_mv Liau, Wei Siang
Zhao, Qiongyi
Bademosi, Adekunle
Gormal, Rachel S.
Gong, Hao
Marshall, Paul R.
Periyakaruppiah, Ambika
Madugalle, Sachithrani U.
Zajaczkowski, Esmi L.
Leighton, Laura J.
Ren, Haobin
Musgrove, Mason
Davies, Joshua
Rauch, Simone
He, Chuan
Dickinson, Bryan C.
Li, Xiang
Wei, Wei
Meunier, Frédéric A.
Fernández Moya, Sandra M.
Kiebler, Michael A.
Srinivasan, Balakumar
Banerjee, Sourav
Clark, Michael
Spitale, Robert C.
Bredy, Timothy W.
author Liau, Wei Siang
author_facet Liau, Wei Siang
Zhao, Qiongyi
Bademosi, Adekunle
Gormal, Rachel S.
Gong, Hao
Marshall, Paul R.
Periyakaruppiah, Ambika
Madugalle, Sachithrani U.
Zajaczkowski, Esmi L.
Leighton, Laura J.
Ren, Haobin
Musgrove, Mason
Davies, Joshua
Rauch, Simone
He, Chuan
Dickinson, Bryan C.
Li, Xiang
Wei, Wei
Meunier, Frédéric A.
Fernández Moya, Sandra M.
Kiebler, Michael A.
Srinivasan, Balakumar
Banerjee, Sourav
Clark, Michael
Spitale, Robert C.
Bredy, Timothy W.
author_role author
author2 Zhao, Qiongyi
Bademosi, Adekunle
Gormal, Rachel S.
Gong, Hao
Marshall, Paul R.
Periyakaruppiah, Ambika
Madugalle, Sachithrani U.
Zajaczkowski, Esmi L.
Leighton, Laura J.
Ren, Haobin
Musgrove, Mason
Davies, Joshua
Rauch, Simone
He, Chuan
Dickinson, Bryan C.
Li, Xiang
Wei, Wei
Meunier, Frédéric A.
Fernández Moya, Sandra M.
Kiebler, Michael A.
Srinivasan, Balakumar
Banerjee, Sourav
Clark, Michael
Spitale, Robert C.
Bredy, Timothy W.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Escorça frontal
Sinapsi
Prefrontal Cortex
Synapses
topic Escorça frontal
Sinapsi
Prefrontal Cortex
Synapses
description 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.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/206244
url https://hdl.handle.net/2445/206244
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1038/s41467-023-43535-1
Nature Communications, 2023, vol. 14, num. 1
https://doi.org/10.1038/s41467-023-43535-1
dc.rights.none.fl_str_mv cc by (c) Liau, Wei Siang et al., 2023
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Liau, Wei Siang et al., 2023
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer Science and Business Media LLC
publisher.none.fl_str_mv Springer Science and Business Media LLC
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869408102952992768
score 15,301603

Similares en LA Referencia