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

Bernat Blasco-Moreno, Leire Campos-Mata, René Böttcher, José García-Martínez, Jennifer Jungfleisch, Danny D. Nedialkova, Shiladitya Chattopadhyay, María-Eugenia Gas, Baldomero Oliva, José E. Pérez-Ortín, Sebastian A. Leidel, Mordechai Choder () and Juana Díez ()
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Bernat Blasco-Moreno: Universitat Pompeu Fabra
Leire Campos-Mata: Universitat Pompeu Fabra
René Böttcher: Universitat Pompeu Fabra
José García-Martínez: Universitat de València
Jennifer Jungfleisch: Universitat Pompeu Fabra
Danny D. Nedialkova: Max Planck Research Group for RNA Biology, Max Planck Institute for Molecular Biomedicine
Shiladitya Chattopadhyay: Technion-Israel Institute of Technology
María-Eugenia Gas: Universitat Pompeu Fabra
Baldomero Oliva: Universitat Pompeu Fabra
José E. Pérez-Ortín: Universitat de València
Sebastian A. Leidel: Max Planck Research Group for RNA Biology, Max Planck Institute for Molecular Biomedicine
Mordechai Choder: Technion-Israel Institute of Technology
Juana Díez: Universitat Pompeu Fabra

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-09199-6

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