Defining the Biology of the ADAR1-RISC Complex

项目摘要 细胞对病毒感染的反应方式对生存至关重要。此外，细胞对 病毒在生命之树上的位置不同，其差异也很大。这一观察表明， 许多成功的策略来抑制病毒感染，就像有许多病毒拮抗剂， 干扰他们。有趣的是，虽然哺乳动物对病毒感染的细胞反应主要是 由I型干扰素（IFN-I）家族介导，我们最近描述了一种IFN-I非依赖性防御 涉及进化保守的RNA酶III核酸酶的系统。我们发现这种叫做Drosha的核酸酶， 在病毒感染时迅速转移到细胞质中并形成高分子量结构 通过与RNA诱导沉默复合物（RISC）结合，我们称之为ADAR-RISC复合物， 或者简单地说ARC。在这里，我们试图更好地了解这种复杂的生理相关性。

PROJECT SUMMARY The means by which cells respond to virus infection is critical for survival. Moreover, the cellular response to virus differs dramatically depending on its position on the tree of life. This observation suggests that there are many successful strategies to inhibit virus infection, just as there are many viral antagonists that have evolved to interfere with them. Interestingly, while the cellular response to virus infection in mammals is primarily mediated by the family of Type I interferons (IFN-I), we recently characterized an IFN-I-independent defense system that involves an evolutionary conserved RNAse III nuclease. We find that this nuclease, called Drosha, rapidly translocates to the cytoplasm in response to virus infection and forms a high molecular weight structure by associating with the RNA-induced silencing complex (RISC) which we have termed the ADAR-RISC Complex or simply, ARC. Here we seek to better understand the physiological relevance of this complex.