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Nonsense-mediated mRNA decay maintains translational fidelity by limiting magnesium uptake

Marcus J O Johansson1, Allan Jacobson

  • 1Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.

Genes & Development
|July 17, 2010
PubMed

Insights

Inactivating yeast nonsense-mediated mRNA decay (NMD) pathway increases magnesium levels, impacting translation termination. This study reveals NMD

Area of Science:

  • Molecular Biology
  • Yeast Genetics
  • RNA Metabolism

Background:

  • The nonsense-mediated mRNA decay (NMD) pathway degrades aberrant mRNAs containing premature translation termination codons.
  • NMD's role in translation termination fidelity is poorly understood, with current hypotheses suggesting direct involvement of NMD factors.

Purpose of the Study:

  • To elucidate the mechanism by which NMD influences translation termination efficiency.
  • To investigate the link between NMD, mRNA stability, and translational fidelity in yeast.

Main Methods:

  • Gene expression analysis of NMD-deficient yeast strains.
  • Measurement of intracellular magnesium (Mg2+) concentrations.
  • Assessment of translation termination efficiency using reporter assays.
  • Analysis of ALR1 mRNA structure and its interaction with the NMD pathway.

Main Results:

  • NMD deficiency leads to increased expression of the magnesium transporter Alr1p.
  • Elevated intracellular Mg2+ levels in NMD-deficient cells reduce translation termination fidelity.
  • An upstream open reading frame (ORF) in ALR1 mRNA targets it for NMD, regulating Alr1p levels.
  • NMD pathway directly impacts cellular Mg2+ homeostasis.

Conclusions:

  • Yeast NMD pathway regulates Mg2+ homeostasis by controlling Alr1p expression.
  • Altered Mg2+ homeostasis in NMD-deficient cells impairs translational fidelity.
  • NMD's influence on translational fidelity is mediated through its control of Mg2+ levels, not direct interaction with termination factors.

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