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响应刺激。最近，人们已经清楚地发现，mRNA稳定性的改变是导致这种快速反应的重要因素。调节脑细胞中信使核糖核酸稳定性的机制还知之甚少。Furneaux博士将研究调节GAP-43mRNA稳定性的因素。GAP-43是一种对神经元功能至关重要的重要蛋白质。Furneaux博士此前克隆了一系列神经元特异性RNA结合蛋白(Elav样蛋白)，它们与GAP-43 mRNA特异结合。在这个项目中，他将检验这样一个假设，即这些蛋白质是调节GAP-43 mRNA稳定性的因素。为了做到这一点，他将使用生化方法。已经建立了一个无细胞体系，可以在体外概括mRNA稳定性的调节。Furneaux博士现在将直接测试添加类Elav蛋白是否会影响GAP-43 mRNA的稳定性。如果假设是正确的，Elav样蛋白可以用来识别这一重要信号通路中的其他成分。此外，他还将研究Elav样蛋白/GAP-43mRNA复合体的结构。这些研究将为Elav样蛋白如何选择性地与GAP-43mRNA结合提供更详细的图景。

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.