脱腺苷酸酶通过调控mRNA的3'-端poly(A)尾巴的长度，广泛参与了mRNA代谢各个环节的调控，具有重要的生理意义。在各种脱腺苷酸酶中，聚腺苷酸专一性核糖核酸酶（PARN）是哺乳动物细胞裂解液中活力最高的脱腺苷酸酶，在高等生物细胞mRNA的代谢调控中起着尤为重要的作用。PARN是一个多结构域的多亚基酶，细胞对PARN有着多层次的调控以实现对特定mRNA翻译效率和代谢的精确控制。最近发现磷酸化会影响PARN参与细胞血清饥饿和DNA损伤时的应答，但磷酸化如何调控PARN参与不同生理活动的分子机制还不清楚，磷酸化在PARN的分子调控中起着什么样的作用也知之甚少。本项目拟在前期工作的基础上，从蛋白和细胞两个水平上，系统研究磷酸化对PARN的结构、酶学性质、蛋白质相互作用和生理功能的影响，从而为更深入探索脱腺苷酸酶通过调控mRNA代谢来参与细胞胁迫应答的分子机制提供新的线索。

Deadenylases are involved in the regulation of mRNA turnover via the regulation of the length of the poly(A) tail at the 3'-end of eukaryotic mRNA. Deadenylase have been found to participate in diverse important physiological processes. Among the various deadenylases, poly(A)-specific ribonuclease has been characterized as the deadenylase with the highest enzymatic activity in higher vertebrates, and is proposed to be crucial to the regulated deadenylation in eukaryotic cells. PARN is a multi-domain/multi-subunit enzyme with the potency to be regulated via diverse factors. Due to the high activity of PARN, the cells are required to control the deadenylase activity of PARN accurately to achieve a precise control of mRNA turnover. Recently, it was found that PARN is a phosphoprotein, and the phosphorylation status affects the participation of PARN in serum starvation/stimulation and DNA damage response processes. However, the mechanisms underlying PARN phosphorylation remain to be elucidated, and the role of phosphorylation in rugulating PARN in diverse physiological processes is also an resolved problem. In this project, we will study the effects of phosphorylation on the structure, enzymatic property, protein-protein interaction and physiological functions of PARN at both the protein and cellular levels. The results are expected to provide new insights into the mechanism of response of the cells to stimuli via regulation of mRNA translational efficiency and decay.