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：
7664925
负责人：
ERIC J WAGNER
金额：
$ 24.9万
依托单位：
UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
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 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7664925
关键词：
Anabolism Award Biochemical Biological Assay Biological Models Cell Culture Techniques Cell Cycle Cell Cycle Arrest Cell Cycle Progression Cells Collaborations Complement Coupled Cultured Cells Disease Double-Stranded RNA Drosophila genus Educational process of instructing Ensure Event Faculty Fellowship G1 Arrest G1 Phase Genes Goals 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 Process Production Proteins RNA RNA Interference Reporter Research Research Personnel Research Project Grants Research Proposals Role Running Screening procedure Signal Transduction Small Nuclear Ribonucleoproteins Tail Testing Training Translations U7 Small Nuclear Ribonucleoprotein Universities Work cancer therapy career development fly genome wide association study genome-wide graduate student knock-down mRNA Export mRNA Precursor member messenger ribonucleoprotein novel programs protein function response retinal rods stem

项目摘要

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 principle 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 DMA 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.

该提案的广泛长期目标是研究参与 3' 末端加工的新因素组蛋白前体 mRNA 以及这些因子如何与细胞周期调节机制进行通讯。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细胞。最近，果蝇组蛋白前体 mRNA 加工所需的新成分已被开发出来。使用全基因组 dsRNA 筛选鉴定，该提案旨在了解这些新蛋白质在果蝇和哺乳动物中都发挥作用。此外，对于已知组件的新颖功能最近发现这一过程在细胞周期进程中发挥着重要作用。这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体 mRNA 加工联系起来。该研究计划的主要研究者的长期目标是进行独立研究终身教职大学教职项目。该研究计划将涉及培训研究生和博士后以及相关的标准教学要求这样的立场。该应用程序对于该职业道路的发展至关重要，因为它包括进一步的培训来自我的导师以及与另一位教职员工的富有成效的合作努力的延续北卡罗来纳大学。了解调节组蛋白生物合成的机制对于理解组蛋白生物合成至关重要与癌症相关的病理学。许多常见的化疗抗癌疗法旨在抑制 DMA 合成。组蛋白合成的抑制应该具有同样有益的结果，因此具有对这一途径的详细了解将增加能够治疗这种疾病的药物库。