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Role of the nonsense-mediated decay factor hUpf3 in the splicing-dependent exon-exon junction complex

V N Kim1, N Kataoka, G Dreyfuss

  • 1Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

Science (New York, N.Y.)
|September 8, 2001
PubMed

Insights

Nonsense-mediated decay (NMD) degrades faulty mRNAs. The protein hUpf3 links mRNA splicing to NMD by binding to spliced mRNAs near exon junctions before they exit the nucleus.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • RNA Metabolism

Background:

  • Nonsense-mediated mRNA decay (NMD) is a crucial cellular surveillance pathway.
  • NMD eliminates mRNAs with premature termination codons (PTCs).
  • This process requires coupling of splicing and translation with translation termination.

Purpose of the Study:

  • To investigate the role of the protein hUpf3 in the NMD pathway.
  • To elucidate the interaction of hUpf3 with mRNA processing and export factors.
  • To understand how hUpf3 connects splicing to NMD.

Main Methods:

  • Co-immunoprecipitation to study protein interactions.
  • Analysis of mRNA-protein complexes.
  • Localization studies of hUpf3 within the cell.

Main Results:

  • hUpf3 interacts with Y14, a component of post-splicing mRNP complexes.
  • hUpf3 is found in mRNP complexes containing mRNA export factors Aly/REF and TAP.
  • hUpf3 binds to spliced mRNAs upstream of exon-exon junctions, similar to Y14 and Aly/REF.

Conclusions:

  • hUpf3 is part of nuclear mRNP complexes destined for export.
  • Splicing-dependent binding of hUpf3 to mRNAs before export links splicing to NMD.
  • hUpf3 acts as a molecular bridge between mRNA splicing and cytoplasmic NMD.

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