烟草花叶病毒RNA 3′-尿苷化修饰的研究

Recently, we cloned a group of novel TMV RNA species with oligo(U)/(U)-rich tails from the TMV-infected hosts including Nicotiana benthamiana and Arabidopsis thaliana. The observation suggested that the TMV RNA underwent 3′-uridylation during the host-TMV interaction. So far, it is known that 3′-uridylation is one of the post-transcriptional RNA modifications and widely exists in eukaryotic cells, playing a positive role in degradation of mRNA and non-coding RNA. However, there is little evidence about 3′-uridylation of the viral RNAs, thus its related mechanism and biological role(s) are under known yet. Therefore, in this study, the experiments will be carried out on the basis of the newly identified 3′-uridylated TMV RNAs as follows: 1) investigating occurrence of the viral RNA uridylation in different virus-host interaction; 2) unravelling the specific nature of the 3′-uridylated TMV RNAs; 3) dissecting the synthesis/decay pathway of the 3′-uridylated TMV RNAs; 4) identifying the possible role(s) of the 3′-uridylated TMV RNAs during the viral life cycle. We believe that the obtained data will not only expand the knowledge of the viral RNAs uridylation, but also disclose the novel interacting between host and virus, thus sheding new light on virology.

在前期研究中，申请者从烟草花叶病毒(TMV) 感染的寄主中克隆了一类新型的病毒RNA分子——具有oligo(U)/(U)-rich尾的TMV RNA，这一结果暗示TMV在与寄主互作过程中，其RNA发生了3′-尿苷化修饰。目前已知，3′-尿苷化是一种重要的RNA转录后修饰方式，在真核生物中广泛发生，具有促进mRNA及非编码RNA降解的功能。但是，病毒RNA的3′-尿苷化修饰迄今鲜有报道，因而其发生机制及在病毒生命活动中的功能均不清楚，有待研究。基于此，本项目拟围绕新发现的3′-尿苷化TMV RNA分子展开，解析病毒RNA发生3′-尿苷化修饰的普遍性，揭示3′-尿苷化病毒RNA的分子特征，探讨其发生及降解的分子途径，最终阐明病毒RNA发生3′-尿苷化的生物学意义。项目预期结果将直接推动目前关于病毒RNA 3′-尿苷化修饰的认知，同时有望揭示寄主-病毒互作的新机制，为病毒学研究提供新思路。

RNA 3'尿苷化在真核生物中普遍存在，但是否在病毒中发生尚不清楚。在本研究中，我们证明了包括真菌病毒、植物病毒和动物病毒等一系列RNA病毒均生成一类迄今未知的RNA分子种群，其3'末端带有oligo（U）或富含U的尾。这一发现表明真核RNA病毒同样广泛存在3′尿苷化。根据此前报道，RNA3'尿苷化是介导真核细胞RNA降解的一种重要机制，由此本研究提出这类此前未知的3′尿苷化病毒RNA分子可能反映了病毒与寄主普遍发生的一种新型互作机制，值得继续深入研究。