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| The EMBO Journal
(1997) 16, 6355–6363, doi:10.1093/emboj/16.21.6355 |
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| Interferon action and apoptosis are defective in mice devoid of 2',5'-oligoadenylate-dependent RNase L |
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| Aimin Zhou1, 2, Jayashree Paranjape1, Thomas L. Brown3, Huiqin Nie1, Sharon Naik1, Beihua Dong1, Ansi Chang4, Bruce Trapp4, Robert Fairchild5, Clemencia Colmenares1 and Robert H. Silverman1, 2 |
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1 Department of Cancer Biology, The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA 2 The Department of Chemistry, Cleveland State University, Cleveland, OH 44115, USA 3 Department of Cell Biology, The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA 4 Department of Neurosciences, The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA 5 Department of Immunology, The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA Received 16 July 1997; Revised 22 August 1997. |
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| Abstract |
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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  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. |
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| Keywords: 2-5A, apoptosis, interferon, RNase L, virus |
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