A dominant negative mutant of 2-5A-dependent RNase suppresses antiproliferative and antiviral effects of interferon.

  • Hassel B
  • Zhou A
  • Sotomayor C
 et al. 
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2-5A-dependent RNase is the terminal factor in the interferon-regulated 2-5A system thought to function in both the molecular mechanism of interferon action and in the general control of RNA stability. However, direct evidence for specific functions of 2-5A-dependent RNase has been generally lacking. Therefore, we developed a strategy to block the 2-5A system using a truncated form of 2-5A-dependent RNase which retains 2-5A binding activity while lacking RNase activity. When the truncated RNase was stably expressed to high levels in murine cells, it prevented specific rRNA cleavage in response to 2-5A transfection and the cells were unresponsive to the antiviral activity of interferon alpha/beta for encephalomyocarditis virus. Remarkably, cells expressing the truncated RNase were also resistant to the antiproliferative activity of interferon. The truncated RNase is a dominant negative mutant that binds 2-5A and that may interfere with normal protein-protein interactions through nine ankyrin-like repeats.

Author-supplied keywords

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Cell Division
  • Cells, Cultured
  • Cloning, Molecular
  • Encephalomyocarditis virus
  • Encephalomyocarditis virus: immunology
  • Endoribonucleases
  • Endoribonucleases: antagonists & inhibitors
  • Endoribonucleases: genetics
  • Endoribonucleases: physiology
  • Enzyme Induction
  • Genes, Dominant
  • Humans
  • Interferons
  • Interferons: biosynthesis
  • Interferons: physiology
  • Mice
  • Molecular Sequence Data
  • Mutation
  • Protein Kinases
  • Protein Kinases: biosynthesis
  • Sequence Homology, Amino Acid
  • Virus Replication

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  • ISSN: 0261-4189
  • SCOPUS: 2-s2.0-0027270867
  • PUI: 23979245
  • PMID: 7688298
  • SGR: 0027270867


  • B A Hassel

  • A Zhou

  • C Sotomayor

  • A Maran

  • R H Silverman

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