真核基因表达存在多层次调控，mRNA稳定性是影响基因表达不容忽视的一个转录后调控环节。 mRNA 3'UTR不稳定元件ARE是导致mRNA不稳定的重要遗传决定因素。已有研究阐述了ARE结合蛋白磷酸化修饰对mRNA稳定性的影响，但mRNA稳定性调节是一个复杂精细的过程，作用机制亟待深入揭示。聚ADP核糖化（PAR化）是一种重要的蛋白翻译后修饰，主要由PARP-1介导。我们前期工作发现PARP-1通过影响mRNA稳定性调节某些促炎基因表达，因此本研究将进一步探究1）mRNA 3'UTR中ARE元件是否是PARP-1顺式作用元件？2）受PARP-1调节的ARE结合蛋白是什么？3）PARP-1与ARE结合蛋白相互作用的分子机制。4）蛋白质PAR化在转录后水平影响促炎基因表达对于机体炎症病理进程的意义。项目的完成将为基因表达转录后调节表观遗传学机制增添新的内容，并揭示PARP-1分子新的生物学功能。

Expressional regulation of eukaryotic genes can be achieved at multiple levels. Besides transcription, mRNA stability provides an additional crucial regulation at the posttranscriptional stage of gene expression. In mRNA stability regulation, some special cis elements harbored in mRNA and the associated trans factors are involved. Among them, AU-rich element (ARE) and ARE-binding proteins have attracted most concern in the studies on mRNA stability. To date, a number of studies elucidated phosphorylation of ARE-binding protein is an important mechanism by which, ARE-binding proteins regulate mRNA stability in response of stimuli. Poly(ADP-ribosyl)ation is also one of the essential posttranslational modification of proteins, catalyzed by PARP family proteins, and of which, PARP-1 is the most important member. Our on-going study showed that PARP-1activation markedly promoted the stability of particular genes' mRNA, however, the precise mechanisms is still unrevealed. The proposed research will clarify 1)whether PARP-1 modulates mRNA stability by acting on mRNA's 3'UTR ARE cis element? 2) What ARE-binding protein(s) are the targets that PARP-1 regulates? 3) What is the molecular mechanisms of PARP-1 interacting with ARE-binding proteins? As well as 4) the implication of PARP-1 regulating the stability of pro-inflammatory genes' mRNA in pathogenensis by utilizing PARP-1 knockout mice and lung-inflammation mice. We anticipate that our data from these studies will help in the understanding of a new epigenetic regulatory mechanism for expression of pro-inflammatory cytokines/chemokines, and will unveal a new biological function of PARP-1.