The exonuclease Xrn1 activates transcription and translation of mRNAs encoding membrane proteins

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  • dc.contributor.author Blasco-Moreno, Bernat
  • dc.contributor.author de Campos-Mata, Leire
  • dc.contributor.author Böttcher, René
  • dc.contributor.author García Martínez, José
  • dc.contributor.author Jungfleisch, Jennifer, 1986-
  • dc.contributor.author Nedialkova, Danny D.
  • dc.contributor.author Chattopadhyay, Shiladitya
  • dc.contributor.author Gas, María-Eugenia
  • dc.contributor.author Oliva Miguel, Baldomero
  • dc.contributor.author Pérez Ortín, José E.
  • dc.contributor.author Leidel, Sebastian
  • dc.contributor.author Choder, Mordechai
  • dc.contributor.author Díez Antón, Juana, 1962-
  • dc.date.accessioned 2019-03-26T09:37:40Z
  • dc.date.available 2019-03-26T09:37:40Z
  • dc.date.issued 2019
  • dc.description.abstract The highly conserved 5’–3’ exonuclease Xrn1 regulates gene expression in eukaryotes by coupling nuclear DNA transcription to cytosolic mRNA decay. By integrating transcriptome-wide analyses of translation with biochemical and functional studies, we demonstrate an unanticipated regulatory role of Xrn1 in protein synthesis. Xrn1 promotes translation of a specific group of transcripts encoding membrane proteins. Xrn1-dependence for translation is linked to poor structural RNA contexts for translation initiation, is mediated by interactions with components of the translation initiation machinery and correlates with an Xrn1-dependence for mRNA localization at the endoplasmic reticulum, the translation compartment of membrane proteins. Importantly, for this group of mRNAs, Xrn1 stimulates transcription, mRNA translation and decay. Our results uncover a crosstalk between the three major stages of gene expression coordinated by Xrn1 to maintain appropriate levels of membrane proteins.
  • dc.description.sponsorship This work was supported by the Spanish Ministry of Economy and Competitiveness (AEI/MINECO/FEDER,UE) through grants BFU2016–80039-R and Unidad de Excelencia Maria de Maeztu funded by the MINECO (ref: MDM-2014–0370) to J.D.; 2017 SGR 909 grant by the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement of the Generalitat de Catalunya to J.D.; EMBO short term fellowship to B.B.-M. (621–2014); 2018FI_B2 00084 grant from the Generalitat de Catalunya to L.D.C.-M.; BFU2016–77728-C3–3-P (MINECO) and PROMETEO II 2015/006 (Regional Valencian Government) to J.E.P.-O.; the Israel Science Foundation to M.C. and by the European Research Council [ERC-2012-StG 310489-tRNAmodi] to S.A.L.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Blasco-Moreno B, de Campos-Mata L, Böttcher R, García-Martínez J, Jungfleisch J, Nedialkova DD, Chattopadhyay S, Gas ME, Oliva B, Pérez-Ortín JE, Leidel SA, Choder M, Díez J. The exonuclease Xrn1 activates transcription and translation of mRNAs encoding membrane proteins. Nature Communications. 2019;10:1298. DOI: 10.1038/s41467-019-09199-6
  • dc.identifier.doi http://dx.doi.org/10.1038/s41467-019-09199-6
  • dc.identifier.issn 2041-1723
  • dc.identifier.uri http://hdl.handle.net/10230/36961
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Nature Communications. 2019;10:1298
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2016–80039-R
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2016–77728-C3–3-P
  • dc.rights © The Author(s) 2019. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Cell biology
  • dc.subject.keyword Molecular biology
  • dc.subject.keyword Ribosome
  • dc.title The exonuclease Xrn1 activates transcription and translation of mRNAs encoding membrane proteins
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion