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

基本信息

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
项目类别：
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

项目摘要

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）：该提案的广泛长期目标是研究组蛋白前MRNA的3'末端处理的新因素，以及这些因素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。最近使用全基因组DSRNA筛选确定了果蝇组蛋白前MRNA所需的新成分，该建议旨在理解这些新蛋白在蝇和哺乳动物中既发挥作用的功能。此外，该过程的已知组成部分的新功能最近被确定为在细胞周期进程中起着至关重要的作用。该建议还将研究这种新功能的性质，以及这如何与组蛋白前MRNA处理联系在一起。该研究计划的主要研究人员的长期目标是在终身教师职位上运行一个独立的研究项目。该研究计划将涉及对研究生和博士后研究员的培训以及与此类职位相关的标准教学要求。该应用对于这一职业道路的发展至关重要，因为它包括我的导师的进一步培训，以及与北卡罗来纳州大学的另一位教职员工进行富有成果的合作努力。了解调节组蛋白生物合成的机制对于了解与癌症相关的病理至关重要。许多常见的化学治疗抗癌疗法旨在抑制DNA合成。抑制组蛋白合成应具有同样有益的结果；因此，对该途径有详细的了解将增加能够治疗该疾病的药物的重复。