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

Nat Commun. 2019 Mar 21;10(1):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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cloning, Molecular
  • Endoplasmic Reticulum / genetics
  • Endoplasmic Reticulum / metabolism
  • Exoribonucleases / genetics*
  • Exoribonucleases / metabolism
  • Gene Expression
  • Gene Expression Profiling
  • Gene Expression Regulation, Fungal*
  • Genetic Vectors / chemistry
  • Genetic Vectors / metabolism
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Protein Biosynthesis*
  • RNA Stability
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Signal Transduction
  • Transcription, Genetic*

Substances

  • Membrane Proteins
  • RNA, Messenger
  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins
  • Exoribonucleases
  • XRN1 protein, S cerevisiae