Puf-Mediated Translation Control in Plasmodium

疟原虫中 Puf 介导的翻译控制

基本信息

批准号：
9314354
负责人：
LIWANG CUI
金额：
$ 36.75万
依托单位：
PENNSYLVANIA STATE UNIVERSITY, THE
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-01 至 2018-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9314354
关键词：
3&apos Untranslated Regions Affect Affinity Chromatography Binding Biological Assay Caenorhabditis elegans Cell-Free System Communicable Diseases Complement Complex Coupled Culicidae Deposition Development Drosophila genus Eukaryota Evolution Family Female Future Gene Expression Gene Expression Profile Genes Genetic Genetic Transcription Human Immunoprecipitation In Vitro Individual Knock-out Lead Life Life Cycle Stages Light Liver Malaria Mass Spectrum Analysis Measures Mediating Messenger RNA Microarray Analysis Molecular Molecular Profiling Morphology Names Nature Parasites Pathway interactions Plasmodium Plasmodium falciparum Play Post-Transcriptional Regulation Process Protein Family Proteins Proteomics RNA RNA Recognition Motif RNA-Binding Proteins Regulation Ribonucleosides Role Salivary Glands Sex Ratio Sexual Development Sporozoites System Technology Therapeutic Intervention Transcript Transfection Translating Translational Regulation Translations Untranslated Regions Work asexual base crosslink design differential expression genetic manipulation genome-wide in vivo insight killings knock-down male member new therapeutic target next generation sequencing novel novel therapeutic intervention overexpression parasite genome premature programs protein complex protein degradation public health relevance trend yeast two hybrid system

项目摘要

DESCRIPTION (provided by applicant): Protein translation is largely unexplored in the malaria parasites. A better understanding of this basic process of life may identify potential targets for developing new therapeutic interventions. Recent studies have revealed the essential roles of translation control during the life cycle of the malaria parasites, especially at the transition stages between the two hosts. The Plasmodium parasite genome encodes four members of Puf RNA-binding proteins, a family of transcript-specific translational regulators in eukaryotes. Puf proteins regulate development by binding to the 3' untranslated regions of the target mRNAs to control their translation. Our recent work shows that a Puf member in P. falciparum is a master regulator of protein translation and plays an important role in regulating sexual development. Based on these observations and different expression profiles of the Puf members in P. falciparum, we hypothesize that the Puf family translational repressors orchestrate parasite development and stage transitions by regulating translation of different sets of genes. To define the roles of Puf proteins in P. falciparum development, we propose to first characterize the functions of individual Puf genes during intraerythrocytic development and stage transitions by genetic knockout or knockdown and determine how the genetic manipulations affect parasite development. We will use complementary approaches to obtain a holistic view of the mRNAs associated with the Puf proteins and to identify pathways that are specifically targeted. The systematic approaches employed in this study will yield comprehensive information about functions of Puf proteins in regulating the developmental cycle of malaria parasites and provide novel insights into the evolution of Puf-mediated translation control in eukaryotes.

描述（由申请人提供）：疟疾寄生虫中的蛋白质翻译在很大程度上尚未被探索。更好地理解这一基本的生命过程可能会确定开发新的治疗干预措施的潜在目标。最近的研究揭示了翻译控制在疟原虫生命周期中的重要作用，特别是在两个宿主之间的过渡阶段。疟原虫寄生虫基因组编码 Puf RNA 结合蛋白的四个成员，Puf RNA 结合蛋白是真核生物中转录特异性翻译调节因子的家族。 Puf 蛋白通过与靶 mRNA 的 3' 非翻译区结合来控制其翻译来调节发育。我们最近的工作表明，恶性疟原虫中的 Puf 成员是蛋白质翻译的主要调节因子，在调节性发育中发挥着重要作用。基于这些观察结果和恶性疟原虫中 Puf 成员的不同表达谱，我们假设 Puf 家族翻译抑制因子通过调节不同基因组的翻译来协调寄生虫的发育和阶段转变。为了确定Puf蛋白在恶性疟原虫发育中的作用，我们建议首先通过基因敲除或敲低来表征单个Puf基因在红细胞内发育和阶段转变过程中的功能，并确定基因操作如何影响寄生虫发育。我们将使用补充方法来全面了解与 Puf 蛋白相关的 mRNA，并确定专门针对的途径。本研究中采用的系统方法将产生有关 Puf 蛋白在调节疟疾寄生虫发育周期中的功能的全面信息，并为真核生物中 Puf 介导的翻译控制的进化提供新的见解。