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

Blasco-Moreno, Bernat; de Campos-Mata, Leire; Böttcher, René; García Martínez, José; Jungfleisch, Jennifer, 1986-; Nedialkova, Danny D.; Chattopadhyay, Shiladitya; Gas, María-Eugenia; Oliva Miguel, Baldomero; Pérez Ortín, José E.; Leidel, Sebastian; Choder, Mordechai; Díez Antón, Juana, 1962-

doi:http://dx.doi.org/10.1038/s41467-019-09199-6

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

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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

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.