Molecular mechanisms of plant defense against pathogens / Mécanismes moléculaires de défense des plantes contre les pathogènes

我们研究了植物抵御病毒的两种分子机制。RNA沉默包括一系列相关过程，通过双链RNA的识别和加工，调节内源基因和外源核酸的基因表达。大多数植物病毒产生双链RNA复制中间体，可被宿主RNA沉默机制靶向。Dicer蛋白将双链RNA加工成确定的小RNA，这些小RNA又与Argonaute （AGO）核糖核酸内切酶结合，该酶靶向并切割互补的单链RNA。同时，植物病毒编码抑制因子或RNA沉默（VSRs），干扰RNA沉默机制。我们开发了一个功能和遗传分析平台，分析拟南芥和其他物种AGO蛋白的抗病毒活性。在此过程中，我们确定了三个关键蛋白，AGO2， AGO4和AGO5靶向病毒rna。特别是，我们发现这些蛋白不仅克服了VSR活性，而且与AGO家族的其他成员不同，它们具有允许它们进入病毒RNA的特性，而病毒RNA通常在病毒复制复合体中受到保护。我们将进行结构-功能，细胞生物学和遗传学分析，以了解某些AGO蛋白如何能够靶向病毒rna以及病毒如何抵消这种防御。此外，我们将研究AGO蛋白的自然变异在确定病毒宿主范围中的作用，其在植物适应性中的作用以及在开发抗病毒植物中的应用。

We study two molecular mechanisms by which plants defend themselves against viruses. RNA silencing encompasses a number of related processes that regulate gene expression of endogenous genes, as well as foreign nucleic acids, through the recognition and processing of double-stranded RNA. Most plant viruses produce double-stranded RNA replication intermediates that can be targeted by the host RNA silencing machinery. Dicer proteins process double-stranded RNAs into defined small RNAs and these in turn are bound by Argonaute (AGO) endoribonucleases that target and cleave complementary single-stranded RNA. At the same time, plant viruses encode suppressors or RNA silencing (VSRs), which interfere with the RNA silencing machinery. We have developed a platform of functional and genetic assays to analyse the antiviral activities of AGO proteins from Arabidopsis thaliana and other species. In doing so, we have identified three key proteins, AGO2, AGO4 and AGO5 that target viral RNAs. In particular, we find that these proteins not only overcome VSR activity, but, unlike other members of the AGO family, they possess properties that allow them to access viral RNA, which is normally protected inside viral replication complexes. We will undertake structure-function, cell biological and genetic analyses to understand how certain AGO proteins are able to target viral RNAs and how viruses counteract this defense. In addition, we will study the role of natural variation in AGO proteins in determining virus host range, its role in plant fitness and its utility in developing virus-resistant plants.