PI: Furneaux IBN-9604174 Furneaux Brain cells respond to stimuli by rapidly changing the expression pattern of a small subset of genes. Recently, it has become clear that the alteration of mRNA stability is an important contributor to this rapid response. The mechanisms that regulate the stability of mRNA in brain cells are poorly understood. Dr. Furneaux will investigate the factors that regulate the stability of GAP-43 mRNA. GAP-43 is an important protein that is crucial for neuronal function. Dr. Furneaux has previously cloned a family of neuronal specific RNA binding proteins (the Elav-like proteins) which specifically bind to GAP-43 mRNA. In this project he will test the hypothesis that these proteins are the factors that regulate GAP-43 mRNA stability. To do this he will use a biochemical approach. A cell-free system has been established that can recapitulate the regulation of mRNA stability in vitro. Dr. Furneaux will now directly test whether the addition of the Elav-like proteins will affect the stability of GAP-43 mRNA. If the hypothesis is correct, the Elav-like proteins can be used to identify other components in this important signaling pathway. In addition he will investigate the structure of the Elav-like protein/GAP-43 mRNA complex. These studies will provide a more detailed picture of how the Elav-like proteins selectively bind to GAP-43 mRNA.