芜菁皱缩病毒编码蛋白抵御宿主无义介导的mRNA降解分子机制研究

无义介导的mRNA降解(NMD)是真核生物重要的抗病毒防御机制之一。病毒是专性寄生生物，尚不明确芜菁皱缩病毒(TCV)编码蛋白可否帮助其耐受或逃避宿主NMD。项目组前期研究发现TCV沉默抑制子P38可抑制拟南芥NMD而提高病毒复制，但分子机制不明确，推测是通过互作劫持宿主NMD因子而发挥作用。此外，不清楚TCV其它编码蛋白是否具有相同功能。本项目拟在此研究基础上开展TCV编码蛋白抵御宿主NMD的分子机制研究，首先筛选鉴定可抑制NMD的TCV编码蛋白；其次鉴定与这些TCV编码蛋白互作的宿主NMD因子，并解析它们互作的分子机制；最后，明确TCV编码蛋白与NMD因子互作对病毒致病性、宿主NMD以及转录后基因沉默(PTGS)途径的影响。研究结果将阐明TCV编码蛋白抑制宿主NMD，增强病毒致病性的分子机制，加深对病毒蛋白功能及宿主PTGS和NMD途径在抗病毒过程中协同作用的认识，为病毒防治提供理论。

Accumulated evidences discovered in recent years reveal that nonsense-mediated mRNA decay (NMD) is one of important antiviral mechanisms for eukaryotes. Viruses are obligatory parasites. It is unclear whether Turnip crinkle virus (TCV) encoded proteins could help virus escape or endure host NMD to establish infection. Our preliminary data shows that P38 which is the suppressor of RNA silencing of TCV plays an important role in counteracting NMD of the plant host to facilitate TCV replication. The central hypothesis of this proposed project is that P38 counteracts NMD by hijacking the players of NMD through interaction. Furthermore, it is unclear whether the other four TCV encoded proteins have the similar function. The specific objective of this proposed project is going to investigate the molecular mechanism of TCV encoded proteins interfering the antiviral RNA degradation of host NMD. To achieve the objective this proposal will employ molecular biology methods, molecular genetics research process as well as biological characteristics to determine the following questions: ① To confirm the interfering effect of P38 protein on NMD and detect whether any other TCV encoded proteins have the same function as well. ② To investigate the proteins in the mRNA decay pathway which interact with those TCV encoded proteins that could interfere host NMD and what is the molecular mechanism of the interaction. ③ How these interactions influence viral replication and pathogenicity as well. ④ How these interactions influence post transcriptional gene silencing pathway and the NMD pathway. The proposed research is innovative because it aspires to unravel a unique function of P38 protein in counteracting mRNA decay to facilitate virus establish infection by interacting with the key players of NMD pathway. It will not only deepen our fundamental understanding how VSRs help viruses increase pathogenicity by inhibiting the antiviral RNA degradation of NMD but also will provide new insights into the concerted function of RNA silencing and RNA decay in plant immunity against exogenous gene transcripts and viral RNA.