The surveillance complex interacts with the translation release factors to enhance termination and degrade aberrant mRNAs

  1. Kevin Czaplinski1,2,
  2. Maria J. Ruiz-Echevarria1,
  3. Sergey V. Paushkin3,
  4. Xia Han1,2,
  5. Youmin Weng1,2,
  6. Haley A. Perlick4,
  7. Harry C. Dietz4,5,
  8. Michael D. Ter-Avanesyan3, and
  9. Stuart W. Peltz1,2,6,7
  1. 1Department of Molecular Genetics and Microbiology and 2Graduate Program in Molecular Biosciences at University of Medicine and Dentistry of New Jersey (UMDNJ)/Rutgers Universities, Robert Wood Johnson Medical School–UMDNJ, 3Institute of Experimental Cardiology, Cardiology Research Center, Moscow, 121552 Russia; 4Department of Pediatrics, Medicine, and Genetics, Center for Medical Genetics, 5Johns Hopkins University School of Medicine, Howard Hughes Medical Institute, Baltimore, Maryland 21205 USA; and 6Cancer Institute of New Jersey, Piscataway, New Jersey 08854 USA

Abstract

The nonsense-mediated mRNA decay pathway is an example of an evolutionarily conserved surveillance pathway that rids the cell of transcripts that contain nonsense mutations. The product of theUPF1 gene is a necessary component of the putative surveillance complex that recognizes and degrades aberrant mRNAs. Recent results indicate that the Upf1p also enhances translation termination at a nonsense codon. The results presented here demonstrate that the yeast and human forms of the Upf1p interact with both eukaryotic translation termination factors eRF1 and eRF3. Consistent with Upf1p interacting with the eRFs, the Upf1p is found in the prion-like aggregates that contain eRF1 and eRF3 observed in yeast [PSI +] strains. These results suggest that interaction of the Upf1p with the peptidyl release factors may be a key event in the assembly of the putative surveillance complex that enhances translation termination, monitors whether termination has occurred prematurely, and promotes degradation of aberrant transcripts.

Keywords

Footnotes

  • 7 Corresponding author.

  • E-MAIL Peltz{at}RWJA.UMDNJ.EDU; FAX (732) 235-5223.

    • Received January 21, 1998.
    • Accepted April 1, 1998.
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