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Updated: Jun 11, 2025

Measurement of mRNA Decay Rates in Saccharomyces cerevisiae Using rpb1-1 Strains
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Published on: December 13, 2014

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Structure of the Nmd4-Upf1 complex supports conservation of the nonsense-mediated mRNA decay pathway between yeast

Irène Barbarin-Bocahu1, Nathalie Ulryck1, Amandine Rigobert1

  • 1Laboratoire de Biologie Structurale de la Cellule (BIOC), CNRS, Ecole polytechnique, Institut Polytechnique de Paris, Palaiseau, France.

Plos Biology
|September 27, 2024
PubMed

Insights

The nonsense-mediated mRNA decay (NMD) pathway

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • The nonsense-mediated mRNA decay (NMD) pathway regulates gene expression by eliminating aberrant mRNAs.
  • The precise NMD mechanism was thought to vary significantly between yeast and metazoans, despite conserved factors like Upf1.
  • The interaction between Upf1 and its partners is crucial for NMD substrate clearance.

Purpose of the Study:

  • To elucidate the structural and functional interactions within the yeast NMD pathway.
  • To investigate the evolutionary conservation of NMD pathway components and mechanisms.
  • To understand how Upf1 interacts with its partners to regulate NMD.

Main Methods:

  • X-ray crystallography to determine the structure of yeast Upf1 bound to Nmd4.
  • Biochemical assays to assess Upf1 ATPase activity and Nmd4's stimulation.
  • Genetic analysis in human cells to evaluate the impact of conserved NMD factor mutations.

Main Results:

  • The crystal structure of yeast Upf1 in complex with Nmd4 was determined.
  • Nmd4 was shown to stimulate Upf1 ATPase activity, facilitating NMD substrate elimination.
  • A conserved interaction region between yeast Nmd4 and metazoan SMG6 with UPF1 was identified, impacting human NMD substrate levels.

Conclusions:

  • The NMD pathway mechanism is universally conserved across eukaryotes.
  • The interaction between Upf1 and its partners, like Nmd4/SMG6, is a conserved feature of NMD.
  • This study provides structural and functional insights into the conserved NMD machinery.

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