An mRNA-binding channel in the ES6S region of the translation 48S-PIC promotes RNA unwinding and scanning

Loading of mRNA onto the ribosomal 43S pre-initiation complex (PIC) and its subsequent scanning require the removal of the secondary structure of the by RNA helicases such as eIF4A. However, the topology and mechanics of the scanning complex bound to mRNA (48S-PIC) and the influence of its solvent-s...

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Detalhes bibliográficos
Autores: Díaz-López, Irene, Toribio, René, Berlanga, Juan José, Ventoso, Iván
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2019
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositório:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/213904
Acesso em linha:http://hdl.handle.net/10261/213904
Access Level:Acceso aberto
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spelling An mRNA-binding channel in the ES6S region of the translation 48S-PIC promotes RNA unwinding and scanningDíaz-López, IreneToribio, RenéBerlanga, Juan JoséVentoso, IvánLoading of mRNA onto the ribosomal 43S pre-initiation complex (PIC) and its subsequent scanning require the removal of the secondary structure of the by RNA helicases such as eIF4A. However, the topology and mechanics of the scanning complex bound to mRNA (48S-PIC) and the influence of its solvent-side composition on the scanning process are poorly known. Here, we found that the ES6S region of the 48S-PIC constitutes an extended binding channel for eIF4A-mediated unwinding of mRNA and scanning. Blocking ES6S inhibited the cap-dependent translation of mRNAs that have structured 5' UTRs (including G-quadruplexes), many of which are involved in signal transduction and growth, but it did not affect IRES-driven translation. Genome-wide analysis of mRNA translation revealed a great diversity in ES6S-mediated scanning dependency. Our data suggest that mRNA threading into the ES6S region makes scanning by 48S PIC slower but more processive. Hence, we propose a topological and functional model of the scanning 48S-PIC.Ministerio de Economıía y Competitividad BFU2013-45003-R ;BFU2017-84955-ReLife Sciences PublicationsMinisterio de Economía y Competitividad (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2020202020192020info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/213904reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.7554/eLife.48246Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2139042026-05-22T06:33:51Z
dc.title.none.fl_str_mv An mRNA-binding channel in the ES6S region of the translation 48S-PIC promotes RNA unwinding and scanning
title An mRNA-binding channel in the ES6S region of the translation 48S-PIC promotes RNA unwinding and scanning
spellingShingle An mRNA-binding channel in the ES6S region of the translation 48S-PIC promotes RNA unwinding and scanning
Díaz-López, Irene
title_short An mRNA-binding channel in the ES6S region of the translation 48S-PIC promotes RNA unwinding and scanning
title_full An mRNA-binding channel in the ES6S region of the translation 48S-PIC promotes RNA unwinding and scanning
title_fullStr An mRNA-binding channel in the ES6S region of the translation 48S-PIC promotes RNA unwinding and scanning
title_full_unstemmed An mRNA-binding channel in the ES6S region of the translation 48S-PIC promotes RNA unwinding and scanning
title_sort An mRNA-binding channel in the ES6S region of the translation 48S-PIC promotes RNA unwinding and scanning
dc.creator.none.fl_str_mv Díaz-López, Irene
Toribio, René
Berlanga, Juan José
Ventoso, Iván
author Díaz-López, Irene
author_facet Díaz-López, Irene
Toribio, René
Berlanga, Juan José
Ventoso, Iván
author_role author
author2 Toribio, René
Berlanga, Juan José
Ventoso, Iván
author2_role author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
description Loading of mRNA onto the ribosomal 43S pre-initiation complex (PIC) and its subsequent scanning require the removal of the secondary structure of the by RNA helicases such as eIF4A. However, the topology and mechanics of the scanning complex bound to mRNA (48S-PIC) and the influence of its solvent-side composition on the scanning process are poorly known. Here, we found that the ES6S region of the 48S-PIC constitutes an extended binding channel for eIF4A-mediated unwinding of mRNA and scanning. Blocking ES6S inhibited the cap-dependent translation of mRNAs that have structured 5' UTRs (including G-quadruplexes), many of which are involved in signal transduction and growth, but it did not affect IRES-driven translation. Genome-wide analysis of mRNA translation revealed a great diversity in ES6S-mediated scanning dependency. Our data suggest that mRNA threading into the ES6S region makes scanning by 48S PIC slower but more processive. Hence, we propose a topological and functional model of the scanning 48S-PIC.
publishDate 2019
dc.date.none.fl_str_mv 2019
2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/213904
url http://hdl.handle.net/10261/213904
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.7554/eLife.48246
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv eLife Sciences Publications
publisher.none.fl_str_mv eLife Sciences Publications
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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