Blasco-Moreno, Bernatde Campos-Mata, LeireBöttcher, RenéGarcía Martínez, JoséJungfleisch, Jennifer, 1986-Nedialkova, Danny D.Chattopadhyay, ShiladityaGas, María-EugeniaOliva Miguel, BaldomeroPérez Ortín, José E.Leidel, SebastianChoder, MordechaiDíez Antón, Juana, 1962-2019-03-262019-03-262019Blasco-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/s41467-019-09199-62041-1723http://hdl.handle.net/10230/36961The 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.application/pdfeng© 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/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41467-019-09199-6Cell biologyMolecular biologyRibosomeinfo:eu-repo/semantics/openAccess