Cross-kingdom RNA communications between plant and fungal pathogens

摘要 真菌病原体感染人类、动物和植物，并造成严重后果 全球人类健康和作物生产。宿主和病原体之间的交流是 对寄主防御和病原菌毒力是必不可少的，但潜在的机制不是 很好理解。我实验室之前的研究发现，一些非编码调控 来自真菌病原体的小RNA(SRNA)，如引起灰色的灰霉病 霉菌病在1000多种植物上传播，可传播到寄主植物细胞和 抑制宿主免疫基因，一种被称为“跨王国RNAi”的机制。最近，我们 发现这样的sRNA交流是双向的。植物寄主也有 发展了主要利用胞外小泡向真菌细胞运送sRNA的能力 并诱导真菌毒力相关基因的跨域RNAi。这样的sna 哺乳动物和寄生虫之间的交流也被观察到。尽管有更多的 跨不同系统的更多研究表明，移动sRNA是关键的调控因素 宿主和病原体相互作用中的分子，跨王国/跨物种RNA领域 沟通仍处于初级阶段。这项建议是为了利用植物拟南芥 和真菌病原菌灰霉菌作为模式系统来解决这方面的突出问题 包括宿主细胞在感染时如何控制sRNA的运输，如何特定的类 小RNA被分选到细胞外小泡中，真菌细胞如何将sRNA运送到 在宿主细胞和真菌中，RNA和囊泡摄取的机制是什么？ 细胞，以及其他类别的RNA，如mRNAs和长的非编码RNA， 在宿主细胞和真菌细胞之间移动，它们在对手方中如何发挥作用等。一个 遗传学、基因组学、生化和分子生物学方法的结合将是 使用。该项目预计将提供前所未有的洞察潜在的 跨王国/跨物种的RNA通信机制，这最终将 帮助开发创新和生态友好的疾病控制战略和基于RNA的 杀菌剂或抗真菌药。

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.