Defining the Biology of the ADAR1-RISC Complex

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.