Nonsense-mediated mRNA decay maintains translational fidelity by limiting magnesium uptake.
Inactivation of the yeast nonsense-mediated mRNA decay (NMD) pathway stabilizes nonsense mRNAs and promotes readthrough of premature translation termination codons. Although the latter phenotype is thought to reflect a direct role of NMD factors in translation termination, its mechanism is unknown. Here we show that the reduced termination efficiency of NMD-deficient cells is attributable to increased expression of the magnesium transporter Alr1p and the resulting effects of elevated Mg(2+) levels on termination fidelity. Alr1p levels increase because an upstream ORF in ALR1 mRNA targets the transcript for NMD. Our results demonstrate that NMD, at least in yeast, controls Mg(2+) homeostasis and, consequently, translational fidelity.
Johansson
Marcus J O
MJ
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
Jacobson
Allan
A
D020121:5' Untranslated Regions; D027682:Cation Transport Proteins / Q000235:genetics; D018389:Codon, Nonsense; D008274:Magnesium / Q000378:metabolism*; D016366:Open Reading Frames; D014176:Protein Biosynthesis; D020871:RNA Stability; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics
D020121:5' Untranslated Regions; C110206:ALR1 protein, S cerevisiae; C110207:ALR2 protein, S cerevisiae; D027682:Cation Transport Proteins; D018389:Codon, Nonsense; D029701:Saccharomyces cerevisiae Proteins; D008274:Magnesium