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

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Nedialkova,  Danny D.
Nedialkova, Danny / Mechanisms of Protein Biogenesis, Max Planck Institute of Biochemistry, Max Planck Society;

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Citation

Blasco-Moreno, B., de Campos-Mata, L., Bottcher, R., Garcia-Martinez, J., Jungfleisch, J., Nedialkova, D. D., et al. (2019). The exonuclease Xrn1 activates transcription and translation of mRNAs encoding membrane proteins. NATURE COMMUNICATIONS, 10: 1298. doi:10.1038/s41467-019-09199-6.


Cite as: http://hdl.handle.net/21.11116/0000-0005-8F0B-F
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. Xrnl-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 Xrnl-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.