The role of host endogenous small RNAs in innate immunity

宿主内源小RNA在先天免疫中的作用

基本信息

批准号：
8280395
负责人：
Hailing Jin
金额：
$ 28.08万
依托单位：
UNIVERSITY OF CALIFORNIA RIVERSIDE
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8280395
关键词：
Animal Model Anti-Bacterial Agents Arabidopsis Bacteria Bacterial Drug Resistance Bacterial Infections Biogenesis Biological Models Biological Process Code DNA Methylation Data Disease Resistance Epigenetic Process Eukaryota F Box Domain Functional RNA Gene Chips Gene Expression Gene Expression Regulation Gene Targeting Genes Genome Host Defense Immune System Diseases Immune response Immune system Immunity Infection Invertebrates Mammals Maps Mediating MicroRNAs Molecular Mouse-ear Cress Natural Immunity Organism Pathway interactions Plants Population Processed Genes Promoter Regions Proteins Pseudomonas syringae RNA Regulation Research Role Shotguns Small Interfering RNA Small RNA System Technology Tissues Transcript Translational Repression Vesicle Work bisulfite chromatin modification chromatin remodeling defense response mRNA Expression mRNA Transcript Degradation pathogen public health relevance response trafficking

项目摘要

DESCRIPTION (provided by applicant): Organisms, including mammals, invertebrates, and plants have evolved sophisticated and conserved innate immune responses to protect themselves from pathogen attacks. In these systems, host immune responses and disease resistance are achieved by modulation of a large array of genes, but how these processes are regulated is still largely unclear. Small RNAs are non-coding regulatory RNA molecules that control gene expression by mediating mRNA degradation, translational inhibition, or chromatin modification. Our work and those of others have demonstrated a role of host endogenous small RNAs, including microRNAs (miRNAs) and small interfering RNAs (siRNAs), in antibacterial innate immunity. We discovered that several pathogen-induced host endogenous siRNAs, including natural antisense transcripts-derived siRNAs (nat-siRNAs) and long siRNAs (lsiRNAs), facilitate host immune responses by posttranscriptionally silencing the negative regulators of plant immune systems. Epigenetic changes were also observed in bacteria-infected plants, however, the role of small RNA-guided DNA methylation and chromatin modification in plant immunity has not been explored. Using Arabidopsis as a model system and Illumina deep sequencing as a platform, we recently profiled the small RNA population after bacterium-challenge and identified diverse classes of endogenous small RNAs that are regulated by the infection of bacterial pathogens. We hypothesize that these pathogen-responsive small RNAs regulate the expression of genes involved in host immune responses by silencing regulators of host immunity transcriptionally or post-transcriptionally. We propose to investigate the regulation, biogenesis, and function of these pathogen-responsive small RNAs. Specifically, we will perform in depth characterization of several newly identified miRNAs, nat-siRNAs, lsiRNAs, and clustered hc-siRNAs that are particularly regulated by various strains of the bacterium Pseudomonas syringae. Predicted target genes of these small RNAs will be validated and subjected to functional analysis. These targets are likely to be components involved in plant immune response pathways. We will also characterize the hc-siRNAs that directed DNA methylation in response to bacterial infection. We will generate a whole-genome DNA-methylation map before and after bacterial infection, and correlate the siRNAs, DNA methylation, and pathogen-responsive gene expression. The proposed research will significantly advance our understanding of the mechanisms and functions of small RNAs involved in host innate immunity. PUBLIC HEALTH RELEVANCE: Multicellular eukaryotes, including mammals, invertebrates, and plants have evolved sophisticated and conserved innate immune responses to protect themselves from pathogen attack. The proposed research will significantly advance our understanding of the mechanisms and function of small RNA-mediated gene regulation in innate immunity using the model organism Arabidopsis thaliana.

描述（由申请人提供）：包括哺乳动物、无脊椎动物和植物在内的生物体已经进化出复杂且保守的先天免疫反应，以保护自身免受病原体攻击。在这些系统中，宿主免疫反应和抗病性是通过调节大量基因来实现的，但这些过程是如何调节的仍不清楚。小RNA是非编码调节RNA分子，通过介导mRNA降解、翻译抑制或染色质修饰来控制基因表达。我们和其他人的工作已经证明了宿主内源性小RNA（包括微小RNA（miRNA）和小干扰RNA（siRNA））在抗菌先天免疫中的作用。我们发现几种病原体诱导的宿主内源siRNA，包括天然反义转录物衍生的siRNA（nat-siRNA）和长siRNA（lsiRNA），通过转录后沉默植物免疫系统的负调节因子来促进宿主免疫反应。在细菌感染的植物中也观察到了表观遗传变化，然而，小RNA引导的DNA甲基化和染色质修饰在植物免疫中的作用尚未被探索。我们最近使用拟南芥作为模型系统和 Illumina 深度测序作为平台，对细菌攻击后的小 RNA 群体进行了分析，并鉴定了受细菌病原体感染调节的不同类别的内源小 RNA。我们假设这些病原体响应性小RNA通过转录或转录后沉默宿主免疫调节因子来调节参与宿主免疫反应的基因的表达。我们建议研究这些病原体反应性小 RNA 的调控、生物发生和功能。具体来说，我们将对几种新鉴定的 miRNA、nat-siRNA、lsiRNA 和簇化 hc-siRNA 进行深入表征，这些 miRNA 特别受到不同丁香假单胞菌菌株的调控。这些小RNA的预测靶基因将得到验证并进行功能分析。这些靶标可能是参与植物免疫反应途径的成分。我们还将表征指导 DNA 甲基化以响应细菌感染的 hc-siRNA。我们将生成细菌感染前后的全基因组 DNA 甲基化图谱，并将 siRNA、DNA 甲基化和病原体反应性基因表达关联起来。拟议的研究将显着增进我们对参与宿主先天免疫的小RNA机制和功能的理解。公共卫生相关性：多细胞真核生物，包括哺乳动物、无脊椎动物和植物，已经进化出复杂且保守的先天免疫反应，以保护自身免受病原体攻击。拟议的研究将显着增进我们对使用模式生物拟南芥的先天免疫中小RNA介导的基因调控机制和功能的理解。