Interferon action and apoptosis are defective in mice devoid of 2',5'-oligoadenylate-dependent RNase L
Interferon action and apoptosis are defective in mice devoid of 2',5'-oligoadenylate-dependent RNase L
复制标题
DOI：
10.1093/emboj/16.21.6355
复制
发表时间：
1997-11-03
期刊：
影响因子：
11.4
通讯作者：
Silverman, RH
中科院分区：
文献类型：
--
作者：
Zhou, AM;Paranjape, J;Silverman, RH
依赖2‘，5’-寡腺苷的核糖核酸酶L在干扰素诱导的核糖核酸衰变途径中发挥作用，称为2-5A系统。为了确定2-5A系统的生理作用，我们用靶向干扰核糖核酸酶L基因的方法制造了小鼠。干扰素a在核糖核酸酶L-/-小鼠体内的抗病毒作用减弱，这首次证明了2-5A系统在动物体内是一种抗病毒途径。此外，核糖核酸酶L-/-小鼠的胸腺明显增大是由于细胞凋亡的抑制，而核糖核酸酶L-/-小鼠的胸腺和脾细胞的凋亡率则减少了2倍。此外，核糖核酸酶L-/-胸腺细胞和成纤维细胞经不同的凋亡剂处理后，细胞的凋亡明显受到抑制，这些结果表明，干扰素的作用和细胞凋亡都可以被核糖核酸酶L控制在核糖核酸稳定的水平上。另外，2-5A系统可能通过诱导感染细胞的凋亡来参与干扰素的抗病毒活性。
2',5'-Oligoadenylate dependent RNase L functions in the interferon-inducibie, 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 a 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.