RNA的降解是基因表达调控的重要内容。AU-rich element （ARE）介导的降解是调控mRNA稳定性的一个关键途径，受到多种因子及多种机制的精确调控。TTP（Tristetraprolin）是较早开始研究的ARE结合蛋白；其对RNA的降解起着重要的调控作用、并且与数种重要的免疫或肿瘤相关基因的mRNA稳定性相关。对TTP蛋白的功能及功能机理已经有所研究，但是现阶段对于TTP蛋白在全基因组水平上的直接的有生理意义的靶标、以及TTP的RNA结合位点还没有系统的认识。进一步研究TTP蛋白在调控RNA稳定性中的作用具有重要的意义。本项目将通过一系列分子生物、生物化学、细胞生物学、生物信息学实验手段，获知TTP蛋白的RNA靶标及其RNA结合位点序列。我们希望结合申请人的工作基础和前期实验数据，扩展对TTP介导的ARE途径调控mRNA和非编码RNA稳定性的认知。

Degradation of RNAs is one of the crucial regulatory events of gene expression. AU-rich element (ARE) mediated degradation is a key pathway in modulating mRNA stability, and this pathway is subjected to the regulation by multiple factors and mechanisms. TTP (Tristetraprolin) is one of the earliest studied ARE binding proteins, and it plays essential roles in the stability of mRNAs of a number of genes related to immunity and tumor. We already have considerable knowledge about functions and functional mechanisms of TTP, although currently we still do not know the genome-wide direct and physiologically important RNA targets, as well as the RNA binding sites of TTP. It is of vital significance to further investigate roles of TTP in the regulation of RNA stability. Under the support of this grant, we will utilize a series of experimental methods in Molecular Biology, Biochemistry, Cell Biology, and Bioinformatics to identify RNA targets and RNA binding sites of TTP. With our research background and indications from the preliminary data, we hope to expand our understandings of TTP mediated part of ARE pathway in the regulation of stability of mRNA and noncoding RNA.