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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.

溶组织内阿米巴原虫是一种重要的人类病原体。E.引起的疾病。