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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.

Citation

Bernat Blasco-Moreno, Leire de 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, Juana Díez. The exonuclease Xrn1 activates transcription and translation of mRNAs encoding membrane proteins. Nature communications. 2019 Mar 21;10(1):1298

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PMID: 30899024

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