6533b872fe1ef96bd12d3978

RESEARCH PRODUCT

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

María-eugenia GasSebastian A. LeidelSebastian A. LeidelMordechai ChoderRené BöttcherShiladitya ChattopadhyayLeire De Campos-mataJosé E. Pérez-ortínJosé García-martínezJuana DíezDanny D. NedialkovaBaldomero OlivaBernat Blasco-morenoJennifer Jungfleisch

subject

0301 basic medicineExonucleaseCell biologySaccharomyces cerevisiae ProteinsTranscription GeneticMolecular biologyScienceRNA StabilityGenetic VectorsGeneral Physics and AstronomyGene Expression02 engineering and technologySaccharomyces cerevisiaeEndoplasmic ReticulumGeneral Biochemistry Genetics and Molecular BiologyArticle03 medical and health sciencesEukaryotic translationTranscription (biology)Gene Expression Regulation FungalGene expression540 ChemistryProtein biosynthesisRNA MessengerCloning Molecularlcsh:ScienceRegulation of gene expressionMultidisciplinarybiologyChemistryGene Expression ProfilingQMembrane ProteinsTranslation (biology)General Chemistry021001 nanoscience & nanotechnologyRibosomeRecombinant Proteins3. Good healthCell biology030104 developmental biologyMembrane proteinProtein BiosynthesisExoribonucleasesbiology.protein570 Life sciences; biologylcsh:Q0210 nano-technologySignal Transduction

description

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.

10.1038/s41467-019-09199-6https://hdl.handle.net/21.11116/0000-0005-8F0B-F21.11116/0000-0005-8F0D-D