MESSENGER RNA DECAY OF IMMEDIATE EARLY GENES

徐博士的这项建议是他从 上一个资助期。他在以下方面取得了重大进展和贡献 对ARE介导的mRNA周转的理解似乎具有所有 为继续这样做做好基础工作。该提案调查了hnRNP D的作用 (也称为AUF1)在含ARE的mRNAs降解中的作用及其方式 翻译后修饰和相关蛋白质会影响这一点。 活动。下面的具体目标旨在获得以下问题的答案 以下问题：1.应激激活信号的作用是什么 途径和泛素-蛋白酶体途径在ARE定向的mRNA转换中？ ARE依赖的mRNA所必需的ARE/蛋白质衰变复合体是什么 周转？3.hnRNP D的哪些结构特征是其发挥作用所必需的 ARE介导的mRNA中的不稳定蛋白在体内衰退？4.ARE是如何发生的 发挥其破坏稳定的作用？调查员建议解决这个问题 通过使用体外RNA衰变系统来解剖和表征问题 ARE靶向的信使核糖核酸衰变。

This proposal by Dr. Shyu is a continuation of his work from the previous funding period. He has made significant progress and contributions to the understanding of ARE-mediated mRNA turnover and appears to have all the groundwork to continue to do so. The proposal investigates the role of hnRNP D (also known as AUF1) in the degradation of ARE-containing mRNAs and how post-translational modifications and associated proteins influence this activity. The specific aims below are designed to obtain answers to the following questions: 1. What are the roles played by stress-activated signaling pathways and the ubiquitin-proteasome pathway in ARE-directed mRNA turnover? 2. What is the ARE/protein decay complex necessary for ARE-dependent mRNA turnover? 3. What structural features of hnRNP D are necessary for its role as a destabilizing protein in ARE-mediated mRNA decay in vivo? 4. How does the ARE exert its destabilizing function? The investigator proposes to address this question by employing in vitro RNA decay systems to dissect and characterize the ARE-targeted mRNA decay.