Characterizing Novel Components Involved in 3' End Processing of Histone pre-mRNA

表征组蛋白前体 mRNA 3 末端加工中涉及的新成分

• 批准号: 7385301
• 负责人: ERIC J WAGNER
• 金额: $ 8.92万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-03 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7385301
• 关键词: Anabolism; Award; Biochemical; Biological Assay; Biological Models; Cell Cycle; Cell Cycle Arrest; Cell Cycle Progression; Cells; Collaborations; Complement; Coupled; Cultured Cells; DNA biosynthesis; DNA chemical synthesis; Development; Disease; Disruption; Double-Stranded RNA; Drosophila genus; Educational process of instructing; Ensure; Event; Faculty; Fellowship; G1 Arrest; G1 Phase; Genes; Genome; Goals; Green Fluorescent Proteins; Heterogeneous Nuclear RNA; Histones; Homologous Gene; Human; Knowledge; Lead; Malignant Neoplasms; Mammals; Mediating; Mediator of activation protein; Mentors; Messenger RNA; Metabolism; Monitor; Nature; North Carolina; Nuclear Extract; Pathology; Pathway interactions; Pharmaceutical Preparations; Phase; Phosphorus; Play; Positioning Attribute; Postdoctoral Fellow; Preparation; Principal Investigator; Process; Production; Proteins; RNA; RNA Interference; Reporter; Research; Research Personnel; Research Project Grants; Research Proposals; Role; Running; Screening procedure; Signal Transduction; Small Nuclear Ribonucleoproteins; Standards of Weights and Measures; Students; Tail; Testing; Training; Translations; U7 Small Nuclear Ribonucleoprotein; Universities; Work; cancer therapy; career; fly; knock-down; mRNA Export; mRNA Precursor; member; messenger ribonucleoprotein; novel; programs; protein function; response; retinal rods; stem

DESCRIPTION (provided by applicant): The broad, long-term goals of this proposal are to study novel factors involved in the 3'-end processing of histone pre-mRNA and how these factors communicate with the cell cycle regulatory machinery. The project will be carried out in two different, yet complementary model systems: Drosophila and mammalian cultured cells. Novel components required for processing of Drosophila histone pre-mRNA have recently been identified using a genome-wide dsRNA screen, and this proposal is aimed at understanding the function that these new proteins play both in flies and mammals. Moreover, a novel function for a known component of this process has been recently identified as playing an essential role in the cell cycle progression. This proposal will also study the nature of this novel function and how this ties into histone pre-mRNA processing. The long-term goal of the principal investigator of this research plan is to run an independent research project in a tenure-track University faculty position. This research program would involve the training of graduate students and postdoctoral fellows as well as the standard teaching requirements associated with such a position. This application is vital to the development of this career path as it includes further training from my mentor as well as a continuation of a fruitful collaborative effort with another faculty member at the University of North Carolina. Understanding the mechanisms regulating the biosynthesis of histones is essential to understand the pathology associated with cancer. Many common chemotherapeutic anti-cancer therapies aim at inhibiting DNA synthesis. Inhibition of histone synthesis should have an equally benefical result; thus having a detailed knowledge of this pathway will increase the repetoire of drugs capable of treating this disease.

描述（由申请人提供）：本提案的广泛，长期目标是研究参与组蛋白前mrna 3'端加工的新因子以及这些因子如何与细胞周期调节机制进行通信。该项目将在两个不同但互补的模型系统中进行：果蝇和哺乳动物培养的细胞。最近，研究者利用全基因组dsRNA筛选技术鉴定出了果蝇组蛋白前mrna加工所需的新组分，这一建议旨在了解这些新蛋白在果蝇和哺乳动物中发挥的功能。此外，该过程的一个已知成分的新功能最近被确定为在细胞周期进程中起重要作用。该提案还将研究这种新功能的性质以及它如何与组蛋白前mrna加工联系在一起。