Structure, dynamics and function of RNA binding proteins

描述（由申请人提供）：基因表达的调节对于有效的生物功能至关重要。该过程的两个关键方面是 mRNA（转录）的合成及其稳定性的控制。该提案的目的是了解一类重要的蛋白质，即三四脯氨酸 (TTP) 家族的 CCCH 锌指蛋白，如何识别并结合 mRNA 以促进其降解。这一过程为减少调节炎症以及癌症发生和进展的关键细胞因子和生长因子的合成提供了重要机制。为了了解 TTP 在细胞中的功能和调节，我们将使用结合核磁共振波谱、计算机模拟、生化和体内实验的综合方法。我们对 TTP-mRNA 相互作用的详细生物物理和生化特征将确定与癌症和炎症相关的 TTP 介导的 mRNA 不稳定的机制。

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.