Argonaute function in Entamoeba histolytica

 描述（由申请方提供）：溶组织内阿米巴是一种原生动物寄生虫，是一种重要的人类病原体。E.溶组织菌包括痢疾和肝脓肿，且该生物体是全球范围内主要寄生虫性死因。基因表达的调节是使寄生虫能够在组织入侵期间适应宿主环境并转化为包囊期并在宿主外传播疾病的关键因素。内阿米巴的基因调控机制之一是一个强大的内源性RNAi途径，它控制与毒力相关的寄生虫基因的表达。然而，由RNAi控制的阿米巴生物学的全部谱尚不清楚，并且对内阿米巴中关于Argonaute蛋白（RNAi途径的主要蛋白质效应物）的知之甚少。在大肠在溶组织阿米巴中，有三个Argonaute家族基因似乎对阿米巴生存力至关重要，并具有不同的细胞定位，暗示了独特的非重叠功能。我们的目的是研究大肠杆菌中的三个Argonaute蛋白。以确定（i）它们是否具有有助于基因沉默的“切割”活性，和（ii）与EhAGO 2 -1和EhAGO 2 -3相关的小RNA群体。这些数据将提高我们对Argonaute蛋白在RNAi中的更广泛范围以及它们在大肠杆菌中的特定作用的理解。溶组织剂我们的工作是在RNA干扰和阿米巴生物学的基本细胞过程的交叉点。出现的数据将有助于理解阿米巴的发病机制，但也扩大了有关RNAi的基本过程的知识。

 DESCRIPTION (provided by applicant): Entamoeba histolytica, a protozoan parasite, is an important human pathogen. Diseases caused by E. histolytica include dysentery and liver abscesses and this 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 endogenous RNAi pathway, which controls expression of parasite genes related to virulence. However, the full repertoire of amebic biology controlled by RNAi is not known and little is known in Entamoeba about Argonaute proteins, the main protein effectors of the RNAi pathway. In E. histolytica, there are three Argonaute family genes that appear essential to amebic viability and have distinct cellular localization, hinting at unique-non overlapping functions. We aim to study the three Argonaute proteins in E. histolytica to determine (i) whether they have "slicing" activity which contributes o gene silencing, and (ii) the small RNA populations that associate with EhAGO2-1 and EhAGO2-3. These data will improve our understanding of the broader scope of Argonaute proteins in RNAi and also their specific roles in E. histolytica. 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.