Structure, dynamics and function of RNA binding proteins

描述（由申请人提供）：基因表达调控是有效生物功能的核心。这一过程的两个关键方面是mRNA的合成（转录）和其稳定性的控制。本研究的目的是了解一类重要的蛋白——三四丙氨酸（TTP）家族的CCCH锌指蛋白是如何识别并结合mRNA以促进其降解的。这一过程为减少关键细胞因子和生长因子的合成提供了重要的机制，这些细胞因子和生长因子调节炎症和癌症的发生和发展。为了了解TTP在细胞中的功能和调控，我们将采用核磁共振光谱、计算机模拟、生化和体内实验相结合的综合方法。我们对TTP-mRNA相互作用的详细生物物理和生化特征将确定ttp介导的mRNA不稳定的机制，这与癌症和炎症有关。

DESCRIPTION (provided by applicant): Regulation of gene expression is central to efficient biological function. Two key aspects of this process are the synthesis of mRNA (transcription) and control of its stability. The goal of this proposal is to understand how an important class of proteins, the CCCH zinc finger proteins of the tristetraprolin (TTP) family, recognizes and binds to mRNA to promote its degradation. This process provides an important mechanism for reducing the synthesis of key cytokines and growth factors that regulate inflammation and the initiation and progression of cancer. To understand the function and regulation of TTP in the cell we will use an integrated approach that combines NMR spectroscopy, computer simulation, biochemical and in vivo experiments. Our detailed biophysical and biochemical characterizations of TTP-mRNA interactions will determine the mechanism of TTP-mediated mRNA destabilization that is relevant for cancer and inflammation.