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Nat Commun. 2019 Mar 21;10(1):1298. doi: 10.1038/s41467-019-09199-6.

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

Author information

1
Virology Unit, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, 08003, Spain.
2
Departments of Genetics, Biochemistry and Molecular Biology, and ERI Biotecmed, Facultad de Biología, Universitat de València, Burjassot, E-46100, Spain.
3
Max Planck Research Group for RNA Biology, Max Planck Institute for Molecular Biomedicine, 48149, Muenster, Germany.
4
Mechanisms of Protein Biogenesis Laboratory, Max Planck Institute of Biochemistry, 82152, Martinsried, Germany.
5
Department of Molecular Microbiology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, 31096, Israel.
6
Laboratory of Structural Bioinformatics (GRIB), Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, 08003, Spain.
7
Department of Chemistry and Biochemistry, University of Bern, Bern, 3012, Switzerland.
8
Department of Molecular Microbiology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, 31096, Israel. choder@technion.ac.il.
9
Virology Unit, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, 08003, Spain. juana.diez@upf.edu.

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.

PMID:
30899024
PMCID:
PMC6428865
DOI:
10.1038/s41467-019-09199-6
[Indexed for MEDLINE]
Free PMC Article

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