The Post-Transcriptional Regulation of GAP-43 Expression

PI：Furneaux IBN-9604174 Furneaux 脑细胞通过快速改变一小部分基因的表达模式来对刺激做出反应。 最近，已经清楚的是，mRNA稳定性的改变是这种快速反应的重要贡献者。 调节脑细胞中mRNA稳定性的机制知之甚少。 Furneaux博士将研究调节GAP-43 mRNA稳定性的因素。 GAP-43是一种重要的蛋白质，对神经元功能至关重要。 Furneaux博士以前克隆了一个神经元特异性RNA结合蛋白（Elav样蛋白）家族，其特异性结合GAP-43 mRNA。 在这个项目中，他将测试这些蛋白质是调节GAP-43 mRNA稳定性的因素的假设。 为此，他将使用生物化学方法。 已经建立了一个无细胞系统，可以概括体外mRNA稳定性的调节。 Furneaux博士现在将直接测试添加Elav样蛋白是否会影响GAP-43 mRNA的稳定性。 如果这一假设是正确的，那么Elav样蛋白可用于鉴定这一重要信号通路中的其他组分。 此外，他还将研究Elav样蛋白/GAP-43 mRNA复合物的结构。 这些研究将为Elav样蛋白如何选择性结合GAP-43 mRNA提供更详细的信息。

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.