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UPF1 association with the cap-binding protein, CBP80, promotes nonsense-mediated mRNA decay at two distinct steps

Jungwook Hwang1, Hanae Sato, Yalan Tang

  • 1Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642, USA.

Molecular Cell
|August 10, 2010
PubMed

Insights

Nonsense-mediated mRNA decay (NMD) is regulated by UPF1 binding to CBP80. Inhibiting this interaction blocks NMD at key steps, revealing a new model for mRNA surveillance.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Nonsense-mediated mRNA decay (NMD) is a crucial surveillance pathway.
  • NMD eliminates aberrant mRNAs with premature termination codons (PTCs).
  • The pioneer round of translation and cap-binding protein complex (CBP80-CBP20) are involved in NMD.

Purpose of the Study:

  • To investigate the role of UPF1 binding to CBP80 in NMD.
  • To elucidate the mechanism by which UPF1 interacts with CBP80 during NMD.
  • To understand how this interaction affects NMD complex formation.

Main Methods:

  • Investigating the interaction between UPF1 and CBP80.
  • Analyzing the impact of inhibiting UPF1-CBP80 binding on NMD.
  • Studying the formation of SURF complexes and exon-junction complexes.

Main Results:

  • Precluding UPF1 binding to CBP80 inhibits NMD at two critical steps.
  • SMG1 and UPF1 association with eukaryotic release factors (eRFs) and exon-junction complexes is impaired.
  • UPF1 binds PTC-containing mRNA more efficiently, a process promoted by the UPF1-CBP80 interaction.

Conclusions:

  • The interaction between UPF1 and CBP80 is essential for efficient NMD.
  • A model of choreographed protein-protein interactions governs NMD on target mRNAs.
  • This study provides new insights into the regulation of mRNA surveillance.

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