Location: Its role in protein-RNA contact during trypanosome gene regulation

位置：锥虫基因调控过程中蛋白质-RNA 接触的作用

基本信息

批准号：
8600785
负责人：
Vivian Bellofatto
金额：
$ 1.24万
依托单位：
UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-06-01 至 2013-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8600785
关键词：
3&apos Untranslated Regions Abbreviations Affect Africa South of the Sahara African Arthropods Awareness Binding Binding Proteins Biochemical Biochemical Genetics Biological Biological Assay Bite Blood Blood Circulation Cardiovascular system Case Study Cell Line Cells Central America Cessation of life Characteristics Code Complex Controlled Study Cytoplasm Data Development Disease Drug Targeting Electrophoretic Mobility Shift Assay Energy Metabolism Environment Enzymes Foundations Fragile X Mental Retardation Protein Gene Expression Gene Expression Profile Gene Expression Regulation Genes Genetic Translation Genomics Glucose Goals Health Human Immunoprecipitation In Vitro Infection Insect Vectors Investigation Laboratories Leishmania Life Cycle Stages Literature Livestock Location Measures Messenger RNA Metabolic Metabolic Pathway Metabolism Middle East Midgut Molecular Genetics Neuraxis Neurobiology Neurons Open Reading Frames Parasites Parasitic infection Pathway interactions Pattern Play Poly(A)+ RNA Polyribosomes Population Process Proliferating Proteins Proteome Publications RNA RNA Binding RNA-Binding Proteins Regulation Role Scanning Seminal South America Southeastern Asia Specificity Staging Structure-Activity Relationship Technology Testing Tissues Translating Translations Trypanosoma Trypanosoma brucei brucei Tsetse Flies Ultraviolet Rays Untranslated Regions Work burden of illness cis acting element crosslink disability-adjusted life years in vivo mRNA Expression mRNA Stability novel protein expression public health relevance research study response synaptic function

项目摘要

DESCRIPTION (provided by applicant): Trypanosomatids are parasites that cause debilitating and often fatal diseases in humans and livestock. A particularly serious problem in sub-Saharan Africa is caused by Trypanosoma brucei, a parasite spread by the bite of an infected Tsetse fly. T. brucei causes disease by proliferating in the blood, tissue spaces, and eventually the central nervous system of its mammalian host. Related parasites are equally important to human populations in other parts of the world, including South and Central America, Southeastern Asia and the Middle East. Our long-term goal is to understand, in biochemical and genetic detail, the mechanisms that coordinate gene expression in trypanosomatids. To achieve this goal, we are specifically investigating the mechanism used by the parasites to regulate their mRNA expression pattern. mRNA expression gives rise to a characteristic and essential proteome and determines the metabolic capabilities of the parasites. As a pathway into understanding mRNA expression control, we are studying a novel RNA-binding protein, RBP42, which was chosen for investigation because it (1) is essential for parasite proliferation and (2) binds to the coding region (open reading frame) of mRNAs encoding a variety of enzymes and proteins within the cells' energy metabolic pathways. We currently know of no other trypanosome protein with this binding specificity; however there is an increasing awareness of coding region binding proteins in the fields of neurobiology and development. Furthermore, our data suggest that RBP42 is an important factor in mRNA translation, mRNA stability or mRNA sequestration as it binds to polysome-associated, translating mRNAs during the procyclic stage of the T. brucei life-cycle. In our aim, we will explore the function of RBP42 by determining its role and mode of action in gene expression networks of T. brucei. This exploratory, two-year project is grounded in preliminary data, in a recent publication from our laboratory, preliminary data and complementary in vivo molecular genetic and in vitro biochemical approaches.

描述（由申请人提供）：锥虫是一种寄生虫，会导致人类和牲畜衰弱甚至致命的疾病。撒哈拉以南非洲地区的一个特别严重的问题是由布氏锥虫引起的，这是一种通过受感染的采采蝇叮咬传播的寄生虫。布氏锥虫通过在哺乳动物宿主的血液、组织空间以及最终的中枢神经系统中增殖而引起疾病。相关寄生虫对世界其他地区的人类同样重要，包括南美洲和中美洲、东南亚和中东。我们的长期目标是从生化和遗传细节上了解锥虫动物基因表达的协调机制。为了实现这一目标，我们正在专门研究寄生虫调节其 mRNA 表达模式的机制。 mRNA 表达产生特征性的必需蛋白质组，并决定寄生虫的代谢能力。作为了解 mRNA 表达控制的途径，我们正在研究一种新型 RNA 结合蛋白 RBP42，选择它进行研究是因为它 (1) 对于寄生虫增殖至关重要，并且 (2) 与编码区（开放阅读框）结合编码细胞能量代谢途径中多种酶和蛋白质的 mRNA。目前我们还不知道其他锥虫蛋白具有这种结合特异性。然而，在神经生物学和发育领域，人们对编码区结合蛋白的认识日益增强。此外，我们的数据表明，RBP42 是 mRNA 翻译、mRNA 稳定性或 mRNA 隔离的重要因素，因为它在 T. brucei 生命周期的前循环阶段与多核糖体相关的翻译 mRNA 结合。我们的目标是，通过确定 RBP42 在 T. brucei 基因表达网络中的作用和作用模式来探索 RBP42 的功能。这个为期两年的探索性项目以我们实验室最近发表的初步数据、初步数据以及补充的体内分子遗传学和体外生化方法为基础。