Trypanosome RNA Binding Proteins

锥虫 RNA 结合蛋白

• 批准号: 6772183
• 负责人: Noreen Williams
• 金额: $ 38.81万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-15 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6772183
• 关键词: RNA binding protein; RNA interference; Trypanosoma brucei; cell line; gene expression; gene targeting; genetic transcription; genetic translation; immunoprecipitation; phenotype; posttranslational modifications; protein quantitation /detection; protein structure function; protozoal genetics; yeast two hybrid system

DESCRIPTION (provided by applicant): The objective of this proposal is to further characterize the function and developmental regulation of two highly related nucleic acid binding proteins, p34 and p37, from the parasitic protozoan, Trypanosoma brucei. We have recently shown that these proteins are associated with 5 S rRNA. We have further shown that these proteins also interact with a family of nucleolar proteins, the NOPP44/46 proteins. These two RNA binding proteins show significant developmental regulation and although the proteins are highly homologous they are regulated by different mechanisms, p34 is predominantly expressed in procyclic forms and is regulated at the level of mRNA stability, p37 is predominantly expressed in the bloodstream stage and is regulated by translational control and protein stability. The specific aims of the project are to: 1. Determine whether the two homologous RNA binding proteins, p34 and p37, have distinct roles in the trypanosome, particularly in light of their differential regulation. 2. Determine the mechanism of posttranscriptional regulation for the expression of the p34 protein. 3. Determine the mechanisms of translational regulation of expression for the p37 protein. These experimental approaches will lead to a better understanding of the function and significance of these two unique nucleic acid binding proteins in cellular RNA processing. Given the developmental nature of their expression, we may find them to be critical to the ability of T. brucei to survive transmission from one host type to another. This may provide a strategic target for chemical intervention.

描述(申请人提供)：这项建议的目的是进一步表征寄生原虫布鲁氏锥虫的两个高度相关的核酸结合蛋白p34和p37的功能和发育调节。我们最近发现这些蛋白与5 S核糖核酸有关。我们进一步表明，这些蛋白还与核仁蛋白家族NOPP44/46蛋白相互作用。这两个RNA结合蛋白显示出显著的发育调节作用，虽然它们高度同源，但它们受到不同机制的调节，p34主要以原环状形式表达，并在mRNA稳定水平上调节，p37主要在血流阶段表达，并受翻译控制和蛋白质稳定性调节。该项目的具体目标是： 1.确定两个同源的RNA结合蛋白p34和p37在锥虫中是否具有不同的作用，特别是根据它们的不同调节。 2.确定转录后调控p34蛋白表达的机制。 3.确定p37蛋白表达的翻译调控机制。 这些实验方法将使我们更好地理解这两种独特的核酸结合蛋白在细胞RNA加工中的功能和意义。考虑到它们表达的发育特性，我们可能会发现它们对布鲁氏毛滴虫从一种宿主类型传播到另一种宿主类型的能力至关重要。这可能为化学干预提供一个战略目标。