Extracellular vesicles, small RNAs, and intercellular communication in Entamoeba histolytica

溶组织内阿米巴的细胞外囊泡、小 RNA 和细胞间通讯

• 批准号: 9165169
• 负责人: UPINDER SINGH
• 金额: $ 19.75万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-10 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9165169
• 关键词: Amoeba genus; Biochemical; Bioinformatics; Biological; Biological Process; Biology; Cause of Death; Cell Communication; Cell Line; Cell physiology; Cells; Cellular biology; Communication; Communities; Complex; Cyst; Data; Data Set; Disease; Dysentery; Enabling Factors; Entamoeba; Entamoeba histolytica; Environment; Exploratory/Developmental Grant; Gene Expression Regulation; Gene Silencing; Gene Silencing Pathway; Generations; Grant; Health; Human; Immune response; Infection; Knowledge; Libraries; Life Cycle Stages; Light; Liver Abscess; Maintenance; Mass Spectrum Analysis; Mediating; MicroRNAs; Molecular; Nematoda; Organism; Parasites; Pathogenesis; Pathway interactions; Plasmodium; Polyphosphates; Polyps; Population; Predisposition; Process; Proteins; RNA Interference; RNA library; RNA-Binding Proteins; Reagent; Regulation; Role; Small RNA; Staging; Structure; System; Tissues; Trichomonas; Virulence; Work; exosome; experience; extracellular; extracellular vesicles; genome-wide; high risk; improved; intercellular communication; interest; member; novel; pathogen; pressure; success; tool; trafficking

Entamoeba histolytica, a protozoan parasite, is an important human pathogen. Diseases caused by E. histolytica include dysentery and liver abscesses, and the organism is a leading parasitic cause of death on a global scale. Regulation of gene expression is a key factor that enables the parasite to adapt to the host environment during tissue invasion and to convert to the cyst stage and propagate disease outside the host. One mechanism of gene regulation in Entamoeba is a robust and complex endogenous RNAi pathway. Over the last several years we have made important observations about this pathway including that small RNAs associate with amebic Argonaute protein to mediate transcriptional gene silencing and have highly unusual 5'- polyP termini. However, despite extensive efforts we have not identified which aspects of amebic biology are regulated by small RNAs, although given that the pathway is maintained in related Entamoeba, a strong evolutionary pressure and clear biological role must exist. We have recently identified that ameba secrete extracellular vesicles that contain small RNAs and RNAi effector proteins. We now seek to determine whether these extracellular vesicles containing small RNAs serve as a means of host-parasite or parasite-parasite intercellular communication. Thus, we will (i) identify small RNA repertoire of amebic extracellular vesicles, (ii) determine if they participate in intercellular communication, and (iii) determine protein components of EVs with focus on RNA binding proteins. These data will improve our understanding of the molecular mechanisms of RNAi in Entamoeba and will also broaden our understanding of the roles of small RNAs in intercellular communication. Our work is at the intersection of the basic cellular process of RNA- interference and amebic biology. Data that emerge will contribute to both understanding amebic pathogenesis but also to expanding the knowledge about the fundamental process of RNAi.

原生动物寄生虫是溶血症，是一种重要的人类病原体。由E引起的疾病 溶组织包括痢疾和肝脓肿，该生物是寄生虫的主要寄生虫病因 全球范围。基因表达的调节是使寄生虫适应宿主的关键因素 组织入侵期间的环境并转化为囊肿阶段并在宿主之外传播疾病。 在ntamoeba中基因调节的一种机制是一种健壮且复杂的内源性RNAi途径。超过 最近几年，我们对这一途径进行了重要的观察，包括小RNA 与Amebic Argonaute蛋白辅助介导转录基因沉默，并具有高度不寻常的5'- 息肉末端。但是，尽管做出了广泛的努力，我们尚未确定Amebic Biology的哪些方面是 受小RNA的调节，尽管鉴于该途径在相关的肠道中保持了，但很强 必须存在进化压力和清晰的生物学作用。我们最近确定了Ameba分泌 包含小RNA和RNAi效应子蛋白的细胞外囊泡。我们现在试图确定是否 这些包含小RNA的细胞外囊泡用作宿主寄生虫或寄生虫寄生虫的一种手段 细胞间沟通。因此，我们将（i）识别小细胞外的小RNA曲目 囊泡，（ii）确定它们是否参与细胞间通信，（iii）确定蛋白质 电动汽车的组成部分，重点是RNA结合蛋白。这些数据将提高我们对 RNAi在Entamoeba中的分子机制，也将扩大我们对小型作用的理解 细胞间通信中的RNA。我们的工作是在RNA-基本细胞过程的交点 干扰和阿米比克生物学。出现的数据将有助于理解Amebic发病机理 还要扩大有关RNAi基本过程的知识。