The role of 2'-5' oligoadenylate-activated ribonuclease L in apoptosis

Cell Death Differ. 1998 Apr;5(4):313-20. doi: 10.1038/sj.cdd.4400352.


Apoptosis of viral infected cells appears to be one defense strategy to limit viral infection. Interferon can also confer viral resistance by the induction of the 2-5A system comprised of 2'-5' oligoadenylate synthetase (OAS), and RNase L. Since rRNA is degraded upon activation of RNase L and during apoptosis and since both of these processes serve antiviral functions, we examined the role RNase L may play in cell death. Inhibition of RNase L activity, by transfection with a dominant negative mutant, blocked staurosporine-induced apoptosis of NIH3T3 cells and SV40-transformed BALB/c cells. In addition, K562 cell lines expressing inactive RNase L were more resistant to apoptosis induced by decreased glutathione levels. Hydrogen peroxide-induced death of NIH3T3 cells did not occur by apoptosis and was not dependent upon active RNAse L. Apoptosis regulatory proteins of the Bcl-2 family did not exhibit altered expression levels in the absence of RNase L activity. RNase L is required for certain pathways of cell death and may help mediate viral-induced apoptosis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Adenine Nucleotides / metabolism*
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Apoptosis / physiology*
  • Cell Line
  • Cell Nucleus / drug effects
  • Cell Nucleus / ultrastructure
  • Endoribonucleases / antagonists & inhibitors
  • Endoribonucleases / genetics
  • Endoribonucleases / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Gene Expression
  • Genes, bcl-2
  • Humans
  • Hydrogen Peroxide / pharmacology
  • K562 Cells
  • Maleates / pharmacology
  • Mice
  • Mutation
  • Oligoribonucleotides / metabolism*
  • Protein Biosynthesis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Staurosporine / pharmacology
  • bcl-2-Associated X Protein
  • bcl-X Protein


  • Adenine Nucleotides
  • BCL2L1 protein, human
  • Bcl2l1 protein, mouse
  • Enzyme Inhibitors
  • Maleates
  • Oligoribonucleotides
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • bcl-X Protein
  • 2',5'-oligoadenylate
  • Hydrogen Peroxide
  • Endoribonucleases
  • 2-5A-dependent ribonuclease
  • diethyl maleate
  • Staurosporine