Interferon action and apoptosis are defective in mice devoid of 2',5'-oligoadenylate-dependent RNase L.
2',5'-Oligoadenylate-dependent RNase L functions in the interferon-inducible, RNA decay pathway known as the 2-5A system. To determine the physiological roles of the 2-5A system, mice were generated with a targeted disruption of the RNase L gene. The antiviral effect of interferon alpha was impaired in RNase L-/- mice providing the first evidence that the 2-5A system functions as an antiviral pathway in animals. In addition, remarkably enlarged thymuses in the RNase L-/- mice resulted from a suppression of apoptosis. There was a 2-fold decrease in apoptosis in vivo in the thymuses and spleens of RNase L-/- mice. Furthermore, apoptosis was substantially suppressed in RNase L-/- thymocytes and fibroblasts treated with different apoptotic agents. These results suggest that both interferon action and apoptosis can be controlled at the level of RNA stability by RNase L. Another implication is that the 2-5A system is likely to contribute to the antiviral activity of interferon by inducing apoptosis of infected cells.
Zhou
A
A
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, OH 44195, USA.
Paranjape
J
J
Brown
T L
TL
Nie
H
H
Naik
S
S
Dong
B
B
Chang
A
A
Trapp
B
B
Fairchild
R
R
Colmenares
C
C
Silverman
R H
RH
D000227:Adenine Nucleotides / Q000494:pharmacology; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D000998:Antiviral Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000502:physiology*; D004686:Encephalomyocarditis virus / Q000187:drug effects; D004722:Endoribonucleases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D016898:Interferon-alpha / Q000494:pharmacology*; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009843:Oligoribonucleotides / Q000494:pharmacology; D009928:Organ Specificity; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000473:pathology; D013950:Thymus Gland / Q000473:pathology; D014779:Virus Replication / Q000187:drug effects
D000227:Adenine Nucleotides; D017304:Annexin A5; D000998:Antiviral Agents; D016898:Interferon-alpha; D009843:Oligoribonucleotides; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; C023505:2',5'-oligoadenylate; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease; D019311:Staurosporine