Argonaute function in Entamoeba histolytica

 描述(申请人提供)：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。由溶组织埃希氏菌引起的疾病包括痢疾和肝脓肿，这种生物是全球范围内主要的寄生性死亡原因。基因表达调控是使寄生虫在组织入侵过程中适应宿主环境，转变为囊肿期并将疾病传播到宿主外的关键因素。内阿米巴基因调控的一个机制是一个强大的内源RNAi途径，它控制着与毒力相关的寄生虫基因的表达。然而，受RNAi控制的阿米巴生物学的完整谱系尚不清楚，在内阿米巴中对RNAi途径的主要蛋白质效应物ArgAerte蛋白知之甚少。在溶组乳杆菌中，有三个Argavit家族基因似乎对阿米巴的生存能力是必不可少的，并且具有不同的细胞定位，暗示着独特的非重叠功能。我们的目标是研究EhAGO2-1和EhAGO2-3的小RNA群体，以确定(I)它们是否具有导致基因沉默的“切片”活性。这些数据将有助于我们更广泛地理解RNAi中Argonaute蛋白的范围，以及它们在溶组织埃希氏菌中的具体作用。我们的工作处于RNA干扰的基本细胞过程和阿米巴生物学的交叉点上。这些数据将有助于理解阿米巴的发病机制，也有助于扩大对RNAi基本过程的了解。

 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.