Cross-kingdom RNA communications between plant and fungal pathogens

总结 真菌病原体感染人类，动物和植物，并对人类造成严重后果。 全球人类健康和作物生产。宿主和病原体之间的通讯是 对宿主防御和病原体毒力至关重要，但其潜在机制不是 很好理解。我实验室以前的研究发现，一些非编码调节 来自真菌病原体的小RNA（sRNA），如灰葡萄孢，它会导致灰色 霉菌病在超过1000种植物上，可以被运送到宿主植物细胞中， 抑制宿主免疫基因，这种机制被称为“跨王国RNAi”。最近我们 发现这种sRNA通讯是双向的。植物宿主也有 开发了主要使用细胞外囊泡将sRNA递送到真菌细胞的能力 并诱导真菌毒力相关基因的跨界RNAi。这种sRNA 哺乳动物和寄生虫之间也有交流。虽然越来越 在不同系统中的更多研究表明，移动的sRNA是关键的调控因子， 宿主和病原体相互作用中的分子，跨王国/跨物种RNA领域 通信仍处于起步阶段。本提案旨在利用植物拟南芥 和真菌病原体葡萄孢属作为一个模型系统，以解决这一悬而未决的问题， 领域，包括，宿主细胞如何控制感染后的sRNA运输，如何特定的类 的小RNA被分选到细胞外囊泡中，真菌细胞如何将sRNA递送到 宿主细胞，RNA和囊泡在宿主细胞和真菌中的摄取机制是什么？ 细胞，以及其他类型的RNA，如mRNA和长非编码RNA， 在宿主和真菌细胞之间移动，它们如何在对方中发挥作用，等等。一 遗传学、基因组学、生物化学和分子生物学方法的结合将是 采用该项目预计将提供前所未有的深入了解的基础 跨王国/跨物种RNA通讯的机制，这将最终 帮助开发创新和生态友好的疾病控制策略， 杀真菌剂或抗真菌药物。

SUMMARY Fungal pathogens infect humans, animals, and plants and cause severe consequences on global human health and crop production. Communication between hosts and pathogens is essential for host defense and pathogen virulence, but the underlying mechanisms are not well understood. Previous studies in my lab discovered that some non-coding regulatory small RNAs (sRNAs) from fungal pathogens, such as Botrytis cinerea, which causes grey mold disease on more than 1000 plant species, can be transported into host plant cells and suppress host immunity genes, a mechanism called “Cross-Kingdom RNAi”. Recently, we discovered that such sRNA communication is bi-directional. Plant hosts have also developed the ability to deliver sRNAs, mainly using extracellular vesicles, to fungal cells and induce cross-kingdom RNAi of fungal virulence-related genes. Such sRNA communication was also observed between mammals and parasites. Although more and more studies across diverse systems demonstrate that mobile sRNAs are key regulatory molecules in host and pathogen interactions, the field of cross-kingdom/cross-species RNA communication is still in its infancy. This proposal is designed to use plant Arabidopsis and fungal pathogen Botrytis as a model system to address the outstanding questions in this field, including, how host cells control sRNA transport upon infection, how specific classes of small RNAs are sorted into extracellular vesicles, how fungal cells deliver sRNAs into host cells, what are the mechanisms of RNA and vesicle uptake in the host cells and fungal cells, and whether other classes of RNAs, such as mRNAs and long non-coding RNAs, move between host and fungal cells, how they function in the counter party, etc.. A combination of genetics, genomics, biochemical and molecular biology approaches will be used. This project is expected to provide unprecedented insight into the underlying mechanisms of cross-kingdom/cross-species RNA communications, which will ultimately help develop innovative and eco-friendly disease control strategies and RNA-based fungicides or antifungal drugs.