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Cx43‐mediated sorting of miRNAs into extracellular vesicles

2022Journal article Restricted access
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dc.contributor.authorMartins Marques, Tânia
dc.contributor.authorCosta, Marina C.
dc.contributor.authorCatarino, Steve
dc.contributor.authorSimões, Isaura
dc.contributor.authorAasen, Trond
dc.contributor.authorEnguita, Francisco J.
dc.contributor.authorGirao, Henrique
dc.date.accessioned2022-05-24T14:53:55Z
dc.date.available2022-05-24T14:53:55Z
dc.date.issued2022
dc.description© 2022 The Authors.pt_PT
dc.description.abstractThrough the exchange of lipids, proteins, and nucleic acids, extracellular vesicles (EV) allow for cell-cell communication across distant cells and tissues to regulate a wide range of physiological and pathological processes. Although some molecular mediators have been discovered, the mechanisms underlying the selective sorting of miRNAs into EV remain elusive. Previous studies demonstrated that connexin43 (Cx43) forms functional channels at the EV surface, mediating the communication with recipient cells. Here, we show that Cx43 participates in the selective sorting of miRNAs into EV through a process that can also involve RNA-binding proteins. We provide evidence that Cx43 can directly bind to specific miRNAs, namely those containing stable secondary structure elements, including miR-133b. Furthermore, Cx43 facilitates the delivery of EV-miRNAs into recipient cells. Phenotypically, we show that Cx43-mediated EV-miRNAs sorting modulates autophagy. Overall, our study ascribes another biological role to Cx43, that is, the selective incorporation of miRNAs into EV, which potentially modulates multiple biological processes in target cells and may have implications for human health and disease.pt_PT
dc.description.sponsorshipThis work was supported by the European Regional Development Fund (ERDF) through the Operational Program for Competitiveness Factors (COMPETE) (under the projects HealthyAging2020 CENTRO-01-0145-FEDER-000012-N2323; CENTRO-01-0145-FEDER-032179, CENTRO-01-0145-FEDER-032414, POCI-01-0145-FEDER-022122, UIDB/04539/2020 and UIDP/04539/2020), COST Action EU-CARDIOPROTECTION, supported by COST (European Cooperation in Science and Technology), Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020) under grant agreement No 952266 (Project RESETageing) and PPBI-Portuguese Platform of BioImaging: POCI-01-0145-FEDER-022122. TA acknowledges funding from Instituto de Salud Carlos III grant PI21/00470 co-financed by the European Regional Development Fund (ERDF), and Fundación Científica Asociación Española Contra el Cáncer (IDEAS SEMILLA AECC 2020/IDEAS20039AASE).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationEMBO Rep. 2022 May 20;e54312pt_PT
dc.identifier.doi10.15252/embr.202154312pt_PT
dc.identifier.eissn1469-3178
dc.identifier.issn1469-221X
dc.identifier.urihttp://hdl.handle.net/10451/53164
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherEMBO Presspt_PT
dc.relationCENTRO-01-0145-FEDER-000012-N2323pt_PT
dc.relationCENTRO-01-0145-FEDER-032179pt_PT
dc.relationCENTRO-01-0145-FEDER-032414pt_PT
dc.relationPOCI-01-0145-FEDER-022122pt_PT
dc.relationCenter for Innovative Biomedicine and Biotechnology
dc.relationCenter for Innovative Biomedicine and Biotechnology
dc.relationRESEarch for healThy AGEING
dc.relation.publisherversionhttps://www.embopress.org/journal/14693178pt_PT
dc.subjectConnexin43pt_PT
dc.subjectHeterogeneous nuclear ribonucleoproteinspt_PT
dc.subjectIntercellular communicationpt_PT
dc.subjectmiRNApt_PT
dc.subjectSelective sortingpt_PT
dc.titleCx43‐mediated sorting of miRNAs into extracellular vesiclespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleCenter for Innovative Biomedicine and Biotechnology
oaire.awardTitleCenter for Innovative Biomedicine and Biotechnology
oaire.awardTitleRESEarch for healThy AGEING
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04539%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04539%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/952266/EU
oaire.citation.titleEMBO reportspt_PT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStreamH2020
person.familyNameCosta
person.familyNameEnguita
person.givenNameMarina
person.givenNameFrancisco J.
person.identifier173306
person.identifier.ciencia-id6818-7810-6CEC
person.identifier.ciencia-idB215-8D49-3218
person.identifier.orcid0000-0001-9020-7539
person.identifier.orcid0000-0002-8072-8557
person.identifier.ridO-1710-2014
person.identifier.ridA-2347-2009
person.identifier.scopus-author-id55453276400
person.identifier.scopus-author-id6602119231
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameEuropean Commission
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
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