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Nonsense-mediated mRNA decay involves two distinct Upf1-bound complexes

Marine Dehecq1,2, Laurence Decourty1, Abdelkader Namane1

  • 1Génétique des Interactions Macromoléculaires, Genomes and Genetics Department, Institut Pasteur, Paris, France.

The EMBO Journal
|October 3, 2018
PubMed

Insights

Nonsense-mediated mRNA decay (NMD) involves two distinct yeast complexes, Upf1-23 and Upf1-decapping. This finding reveals conserved NMD mechanisms across eukaryotes, aiding further research.

Area of Science:

  • Molecular Biology
  • RNA Biology
  • Cellular Mechanisms

Background:

  • Nonsense-mediated mRNA decay (NMD) is a critical RNA surveillance pathway.
  • NMD regulates gene expression, telomere maintenance, and embryo development.
  • Core NMD factors (Upf1, Upf2, Upf3) are conserved, but a universal model is lacking.

Purpose of the Study:

  • To characterize the composition and dynamics of yeast NMD complexes.
  • To elucidate the functional roles of identified NMD factors.
  • To propose a conserved model for NMD mechanism.

Main Methods:

  • Affinity purification coupled with mass spectrometry in yeast.
  • Utilized an improved data analysis protocol for complex identification.
  • Investigated protein-protein and protein-RNA interactions within NMD complexes.

Main Results:

  • Identified two distinct Upf1-associated complexes: Upf1-23 and Upf1-decapping.
  • Upf1-decapping complex contains the mRNA decapping enzyme, Nmd4, and Ebs1.
  • Nmd4 and Ebs1 are critical for RNA degradation and their association depends on Upf1-23 components.

Conclusions:

  • Yeast NMD operates through successive Upf1-23 and Upf1-decapping complexes.
  • Nmd4/Ebs1 proteins show similarity to mammalian Smg5-7, suggesting conserved NMD mechanisms.
  • The proposed model provides a framework for studying NMD in eukaryotes.
Keywords:
NMDSaccharomyces cerevisiaeRNA decayaffinity purificationquantitative mass spectrometry

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