Modification and dynamic regulation of Argonaute proteins-the key small RNA pathway components in host innate immunity

Argonaute蛋白的修饰和动态调控——宿主先天免疫中关键的小RNA通路成分

• 批准号: 9231457
• 负责人: Hailing Jin
• 金额: $ 31.06万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9231457
• 关键词: Agriculture; Animal Model; Animals; Anti-Bacterial Agents; Antibodies; Antifungal Agents; Arabidopsis; Arginine; Bacterial Infections; Binding; Biological Assay; Botrytis; Catalytic Domain; Cells; Co-Immunoprecipitations; Complement; Coupled; Detection; Eukaryota; Fluorescence; Funding; Gene Silencing; Genes; Goals; Health; Human; Immune response; Immune system; Immunity; In Vitro; Infection; Innate Immune System; Invertebrates; Knock-out; Mammals; Mass Spectrum Analysis; Mediating; Methylation; Modification; Mouse-ear Cress; Mutation; Natural Immunity; Organism; Output; Pathway interactions; Phosphoric Monoester Hydrolases; Phosphorylation Site; Plant Model; Plants; Play; Protein Family; Protein Phosphatase 2A Regulatory Subunit PR53; Protein phosphatase; Protein-Arginine N-Methyltransferase; Proteins; Proteomics; Pseudomonas syringae; RNA Helicase; RNA Interference; RNA Interference Pathway; Regulation; Research; Role; Site; Small RNA; System; Testing; United States National Institutes of Health; Untranslated RNA; Viral; Virulence; Work; dimethylarginine; disorder control; helicase; in vivo; mutant; novel; pathogen; protein phosphatase 2C; public health relevance

 DESCRIPTION (provided by applicant): Eukaryotic organisms, including animals and plants, have evolved sophisticated immune systems to protect themselves against pathogens. Small RNAs (sRNAs) are short, non-coding regulatory RNAs that induce RNA interference (RNAi) by binding to Argonaute (AGO) proteins and directing silencing of genes with complementary sequences. Our work and those of others have demonstrated that sRNAs, derived from either hosts or pathogens, function through AGO proteins and play an important role in host-pathogen interactions. However, the underlying regulatory mechanisms remain elusive. Our long-term goal is to understand the dynamic regulation of sRNAs and RNAi in host innate immunity. AGO proteins are key players of sRNA- mediated gene silencing, and we hypothesize that they are modified and regulated by their associated proteins to modulate sRNA-mediated gene silencing. Here, we seek to understand the modification and regulation of AGOs in RNAi pathway, and in host antibacterial and antifungal immune responses, by using model plant-pathogen interaction systems - Arabidopsis thaliana and its bacterial pathogen Pseudomonas syringae and aggressive fungal pathogen Botrytis cinerea. During the last funding period, we have identified diverse classes of host sRNAs regulating host immunity, and have demonstrated that Arabidopsis AGO2 (AtAGO2) is highly induced by bacterial infection and positively regulates host immunity. We have also shown that B. cinerea delivers its sRNAs into host cells and hijacks host AtAGO1 to suppress host immunity genes for successful infection. To obtain a mechanistic understanding of how AtAGO1 and AtAGO2 are regulated, we have identified their associated proteins via proteomics analysis. This renewal will study the modification and regulation of AtAGO1 and AtAGO2 by their associated proteins in RNAi pathways and host innate immunity. The output of this study will significantly advance our understanding of dynamic control of RNAi in host immune responses against pathogens, which will have great impact on both agricultural and human health. The specific aims are: 1. Elucidate the role of protein arginine methyltransferases in modification and regulation of AtAGO function in host immunity. 2. Investigate the function of DDX3-like RNA helicases in modulating AtAGO function in host immunity. 3. Study the role of protein phosphatases in modulating AtAGO and host immunity.