A reconstituted mammalian APC-kinesin complex selectively transports defined packages of axonal mRNAs

Through the asymmetric distribution of messenger RNAs (mRNAs), cells spatially regulate gene expression to create cytoplasmic domains with specialized functions. In neurons, mRNA localization is required for essential processes such as cell polarization, migration, and synaptic plasticity underlying...

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Autores: Baumann, Sebastian, Komissarov, Artem, 1992-, Gili, Maria, Ruprecht, Verena, Wieser, Stefan, Maurer, Sebastian
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/44497
Acesso em linha:http://hdl.handle.net/10230/44497
http://dx.doi.org/10.1126/sciadv.aaz1588
Access Level:acceso abierto
Palavra-chave:RNA missatger
Genètica
Genòmica
Tumors
Proteïnes
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spelling A reconstituted mammalian APC-kinesin complex selectively transports defined packages of axonal mRNAsBaumann, SebastianKomissarov, Artem, 1992-Gili, MariaRuprecht, VerenaWieser, StefanMaurer, SebastianRNA missatgerGenèticaGenòmicaTumorsProteïnesThrough the asymmetric distribution of messenger RNAs (mRNAs), cells spatially regulate gene expression to create cytoplasmic domains with specialized functions. In neurons, mRNA localization is required for essential processes such as cell polarization, migration, and synaptic plasticity underlying long-term memory formation. The essential components driving cytoplasmic mRNA transport in neurons and mammalian cells are not known. We report the first reconstitution of a mammalian mRNA transport system revealing that the tumor suppressor adenomatous polyposis coli (APC) forms stable complexes with the axonally localized β-actin and β2B-tubulin mRNAs, which are linked to a kinesin-2 via the cargo adaptor KAP3. APC activates kinesin-2, and both proteins are sufficient to drive specific transport of defined mRNA packages. Guanine-rich sequences located in 3'UTRs of axonal mRNAs increase transport efficiency and balance the access of different mRNAs to the transport system. Our findings reveal a minimal set of proteins sufficient to transport mammalian mRNAs.This work was funded by the Spanish Ministry of Economy and Competitiveness (MINECO) (BFU2017-85361-P, BFU2014-54278-P, and BFU2015-62550-ERC), Juan de la Cierva-Incorporación Program (IJCI-2015-25994), the Human Frontiers in Science Program (HFSP) (RGY0083/2016), and the European Research Council (ERC) (H2020-MSCA-IF-2014-659271). V.R. acknowledges support from the Spanish Ministry of Economy and Competitiveness through the Program “Centro de Excelencia Severo Ochoa 2013–2017,” the CERCA Programme/Generalitat de Catalunya, MINECO’s Plan Nacional (BFU2017-86296-P). S.W. acknowledges support from the Spanish Ministry of Economy and Competitiveness through the “Severo Ochoa” program for Centres of Excellence in R&D (SEV-2015-0522), from Fundació Privada Cellex, and from Generalitat de Catalunya through the CERCA program. We further acknowledge support of the Spanish Ministry of Economy and Competitiveness (MEIC) to the EMBL partnership, “Centro de Excelencia Severo Ochoa” (SEV-2012-0208) and the CERCA Programme/Generalitat de CatalunyaAmerican Association for the Advancement of Science (AAAS)202020202020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/44497http://dx.doi.org/10.1126/sciadv.aaz1588reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésScience Advances. 2020 Mar 13;6(11):eaaz1588info:eu-repo/grantAgreement/EC/H2020/659271info:eu-repo/grantAgreement/ES/1PE/BFU2014-54278-Pinfo:eu-repo/grantAgreement/ES/1PE/BFU2015-62550-ERCinfo:eu-repo/grantAgreement/ES/2PE/ BFU2017-85361-Pinfo:eu-repo/grantAgreement/ES/2PE/ BFU2017-86296-P© 2020 by Sebastian Baumann et al., some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC)http://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/444972026-05-29T05:05:01Z
dc.title.none.fl_str_mv A reconstituted mammalian APC-kinesin complex selectively transports defined packages of axonal mRNAs
title A reconstituted mammalian APC-kinesin complex selectively transports defined packages of axonal mRNAs
spellingShingle A reconstituted mammalian APC-kinesin complex selectively transports defined packages of axonal mRNAs
Baumann, Sebastian
RNA missatger
Genètica
Genòmica
Tumors
Proteïnes
title_short A reconstituted mammalian APC-kinesin complex selectively transports defined packages of axonal mRNAs
title_full A reconstituted mammalian APC-kinesin complex selectively transports defined packages of axonal mRNAs
title_fullStr A reconstituted mammalian APC-kinesin complex selectively transports defined packages of axonal mRNAs
title_full_unstemmed A reconstituted mammalian APC-kinesin complex selectively transports defined packages of axonal mRNAs
title_sort A reconstituted mammalian APC-kinesin complex selectively transports defined packages of axonal mRNAs
dc.creator.none.fl_str_mv Baumann, Sebastian
Komissarov, Artem, 1992-
Gili, Maria
Ruprecht, Verena
Wieser, Stefan
Maurer, Sebastian
author Baumann, Sebastian
author_facet Baumann, Sebastian
Komissarov, Artem, 1992-
Gili, Maria
Ruprecht, Verena
Wieser, Stefan
Maurer, Sebastian
author_role author
author2 Komissarov, Artem, 1992-
Gili, Maria
Ruprecht, Verena
Wieser, Stefan
Maurer, Sebastian
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv RNA missatger
Genètica
Genòmica
Tumors
Proteïnes
topic RNA missatger
Genètica
Genòmica
Tumors
Proteïnes
description Through the asymmetric distribution of messenger RNAs (mRNAs), cells spatially regulate gene expression to create cytoplasmic domains with specialized functions. In neurons, mRNA localization is required for essential processes such as cell polarization, migration, and synaptic plasticity underlying long-term memory formation. The essential components driving cytoplasmic mRNA transport in neurons and mammalian cells are not known. We report the first reconstitution of a mammalian mRNA transport system revealing that the tumor suppressor adenomatous polyposis coli (APC) forms stable complexes with the axonally localized β-actin and β2B-tubulin mRNAs, which are linked to a kinesin-2 via the cargo adaptor KAP3. APC activates kinesin-2, and both proteins are sufficient to drive specific transport of defined mRNA packages. Guanine-rich sequences located in 3'UTRs of axonal mRNAs increase transport efficiency and balance the access of different mRNAs to the transport system. Our findings reveal a minimal set of proteins sufficient to transport mammalian mRNAs.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020
2020
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 http://hdl.handle.net/10230/44497
http://dx.doi.org/10.1126/sciadv.aaz1588
url http://hdl.handle.net/10230/44497
http://dx.doi.org/10.1126/sciadv.aaz1588
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Science Advances. 2020 Mar 13;6(11):eaaz1588
info:eu-repo/grantAgreement/EC/H2020/659271
info:eu-repo/grantAgreement/ES/1PE/BFU2014-54278-P
info:eu-repo/grantAgreement/ES/1PE/BFU2015-62550-ERC
info:eu-repo/grantAgreement/ES/2PE/ BFU2017-85361-P
info:eu-repo/grantAgreement/ES/2PE/ BFU2017-86296-P
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Association for the Advancement of Science (AAAS)
publisher.none.fl_str_mv American Association for the Advancement of Science (AAAS)
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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