Small RNA regulation of gene expression in Entamoeba

内阿米巴基因表达的小RNA调控

基本信息

批准号：
9283327
负责人：
UPINDER SINGH
金额：
$ 62.33万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-06-01 至 2021-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9283327
关键词：
Amoeba genus Antibodies Binding Biogenesis Biological Models Biological Process Biology Cause of Death Cell physiology Cells Communities Complex Data Disease Dominant Genetic Conditions Dominant-Negative Mutation Dysentery Entamoeba Entamoeba histolytica Environment Epigenetic Process Eukaryota Funding Gene Expression Gene Expression Regulation Gene Silencing Generations Genes Genetic Transcription Goals Grant Health Heat-Shock Response Histones Human Knowledge Life Liver Abscess Mediating Messenger RNA Methods Modification Molecular NUP214 gene Nematoda Nuclear Organism Oxidative Stress Parasites Pathogenesis Pathway interactions Polynucleotide Adenylyltransferase Polyps Population Predisposition Process Proteins Protozoa Published Comment RNA Binding RNA Interference RNA Interference Pathway RNA-Induced Silencing Complex Reagent Resistance Role Small RNA System Tissues Virulence Work base calreticulin chromatin immunoprecipitation exosome experience genetic approach genetic manipulation genome-wide histone modification improved interest member novel particle pathogen protein complex resistance gene success tool transcriptome sequencing

项目摘要

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 between life stages to 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 amebic small RNAs have highly unusual 5'-polyP termini and associate with amebic Argonaute 2-2 protein to mediate transcriptional gene silencing. Additionally, we identified that Entamoeba contains three Argonaute proteins with different cellular localizations and apparently non-redundant functions. We have also used information on the amebic RNAi pathway to develop a novel and robust gene-silencing tool in Entamoeba based on use of a “trigger” gene. Trigger gene silencing is highly robust and stable and is mediated by repressive histone modifications on the trigger-silenced loci. Our goal is to focus on aspects of RNAi in ameba that are either unique compared to other systems or which intersect with important aspects of parasite biology. Thus, we will (i) determine the molecular mechanisms of small RNA “trigger” mediated gene silencing, and (ii) characterize the components of the Argonaute RNA induced silencing complexes. These data will improve our understanding of the molecular mechanisms of RNAi in Entamoeba. 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 a basic process in amebic biology and to expanding the knowledge about the fundamental process of RNAi.

溶组织内阿米巴（Entamoeba histolytica）是一种原生动物寄生虫，是由阿米巴引起的重要人类疾病。溶组织病包括痢疾和肝脓肿，该微生物是导致动物死亡的主要原因全球范围内基因表达的调控是寄生虫适应宿主的关键因素。组织侵入期间的环境以及在生命阶段之间转换以在宿主体外传播疾病。内阿米巴基因调控的一种机制是强大而复杂的内源性 RNAi 途径。在过去的几年里，我们对这条途径进行了重要观察，包括阿米巴小 RNA 具有非常不寻常的 5'-polyP 末端，并与阿米巴 Argonaute 2-2 蛋白结合以介导此外，我们还发现内阿米巴含有三种 Argonaute 蛋白。具有不同的细胞定位和明显非冗余的功能我们还使用了以下信息。阿米巴 RNAi 途径，基于使用 “触发”基因沉默是高度稳健和稳定的，由抑制性组蛋白介导。我们的目标是关注阿米巴 RNAi 的以下方面。与其他系统相比是独一无二的，或者与寄生虫生物学的重要方面相交叉，因此，我们将。 (i) 确定小 RNA“触发”介导的基因沉默的分子机制，以及 (ii) 这些数据将表征 Argonaute RNA 诱导的沉默复合物的成分。提高我们对内阿米巴 RNAi 分子机制的理解。 RNA 干扰的基本细胞过程和阿米巴生物学的交叉点即将出现的数据。有助于理解阿米巴生物学的基本过程，并扩大有关阿米巴生物学的知识 RNAi的基本过程。