Structural basis for the biological relevance of the invariant apical stem in IRES-mediated translation

Fernandez, Noemí; Fernandez Miragall, Olga; Ramajo, Jorge; García Sacristán, Ana; Bellora Pereyra, Nicolás; Eyras Jiménez, Eduardo; Briones, Carlos; Martinez Salas, Encarnación

Structural basis for the biological relevance of the invariant apical stem in IRES-mediated translation

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dc.contributor.author Fernandez, Noemíca
dc.contributor.author Fernandez Miragall, Olgaca
dc.contributor.author Ramajo, Jorgeca
dc.contributor.author García Sacristán, Anaca
dc.contributor.author Bellora Pereyra, Nicolásca
dc.contributor.author Eyras Jiménez, Eduardoca
dc.contributor.author Briones, Carlosca
dc.contributor.author Martinez Salas, Encarnaciónca
dc.date.accessioned 2015-04-07T09:36:03Z
dc.date.available 2015-04-07T09:36:03Z
dc.date.issued 2011ca
dc.description.abstract RNA structure plays a fundamental role in internal initiation of translation. Picornavirus internal ribosome entry site (IRES) are long, efficient cis-acting elements that recruit the ribosome to internal mRNA sites. However, little is known about long-range constraints determining the IRES RNA structure. Here, we sought to investigate the functional and structural relevance of the invariant apical stem of a picornavirus IRES. Mutation of this apical stem revealed better performance of G:C compared with C:G base pairs, demonstrating that the secondary structure solely is not sufficient for IRES function. In turn, mutations designed to disrupt the stem abolished IRES activity. Lack of tolerance to accept genetic variability in the apical stem was supported by the presence of coupled covariations within the adjacent stem–loops. SHAPE structural analysis, gel mobility-shift and microarrays-based RNA accessibility revealed that the apical stem contributes to maintain IRES RNA structure through the generation of distant interactions between two adjacent stem–loops. Our results demonstrate that a highly interactive structure constrained by distant interactions involving invariant G:C base pairs plays a key role in maintaining the RNA conformation necessary for IRES-mediated translation.en
dc.description.sponsorship Grants from Ministerio de Ciencia e Innovación (BFU2008-02159, CSD2009-00080 to E.M.S.); Institutional grant from Fundación Ramón Areces. Work at Universitat Pompeu Fabra was supported by grant BIO2008-01091. Work at Centro de Astrobiologia was supported by grants BIO2007-67523, BIO2010-20696, EUI2008-00158; CSIC (grant 200920I040); European Union and Comunidad de Madrid. CIBERehd is funded by the Instituto de Salud Carlos III. Funding for open access charge: CSD-2009-0080, BFU2008-02159en
dc.format.mimetype application/pdfca
dc.identifier.citation Fernandez N, Fernandez-Miragall O, Ramajo J, Garcia-Sacristan A, Eyras E, Bellora N et al. Structural basis for the biological relevance of the invariant apical stem in IRES-mediated translation. Nucleic Acids Research. 2011;39(19):8572-85. DOI: 10.1093/nar/gkr560ca
dc.identifier.doi http://dx.doi.org/10.1093/nar/gkr560
dc.identifier.issn 0305-1048ca
dc.identifier.uri http://hdl.handle.net/10230/23339
dc.language.iso engca
dc.publisher Oxford University Pressca
dc.relation.ispartof Nucleic Acids Research. 2011;39(19):8572-85
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2008-02159
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BIO2008-01091
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/CSD2009-00080
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PN/BIO2007-67523
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/EUI2008-00158
dc.rights © Fernandez N, Fernandez-Miragall O, Ramajo J, Garcia-Sacristan A, Eyras E, Bellora N, Briones C, Martinez-Salas E [2011]. Published by Oxford University Press. This is an Open Access article distributed under the terms of a Creative Commons Attribution Licenseca
dc.rights.accessRights info:eu-repo/semantics/openAccessca
dc.rights.uri http://creativecommons.org/licenses/by-nc/3.0
dc.subject.other RNA missatgerca
dc.subject.other Seqüència de nucleòtidsca
dc.title Structural basis for the biological relevance of the invariant apical stem in IRES-mediated translationen
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/publishedVersionca

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