How Cyclophilins Both Regulate and Are Regulated by RNA

Cyclophilins are a family of protein chaperones and signaling molecules found in every domain of life. In humans, they play key roles in numerous signaling pathways and contribute to several pathologies including roles in viral life cycles such as HIV, measles, Hep C, as well as many other pathogens relevant to human health. In addition cyclophilins play roles in inflammation and cancer and are already the target of several clinical drugs such as cyclosporin A. Surprisingly, this family has been robustly identified as novel RNA-binding proteins in numerous crosslinking studies. Subsequent validation of these interactions and the additional observation that RNA impacts the enzymatic activity of several cyclophilins provides a wholly new avenue of study to understand how cyclophilins are regulated and how they regulate key cellular processes. The goal of this research project is to identify the specific RNA molecules these proteins bind, what that binding interface looks like, and to determine the role(s) of these interactions in cyclophilin biology. This work will significantly advance the understanding of the emerging mechanisms that RNAs use to regulate protein activity. In addition, the tools developed will benefit studies by others that seek to understand the full array of RNA/protein interactions.