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

该提案的广泛的长期目标是研究参与3'末端加工的新因素， 组蛋白前mRNA以及这些因子如何与细胞周期调节机制进行通信。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 细胞果蝇组蛋白前体mRNA加工所需的新组分最近被发现， 使用全基因组dsRNA筛选鉴定，该建议旨在了解 这些新的蛋白质在苍蝇和哺乳动物中都发挥作用。此外，一个新的函数的一个已知的组件， 该过程最近被鉴定为在细胞周期进程中起重要作用。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mRNA加工联系在一起。 本研究计划的主要研究者的长期目标是进行独立研究 项目在大学终身教职的位置。这项研究计划将包括培训 研究生和博士后研究员以及与之相关的标准教学要求 这样的立场。该应用程序对这一职业道路的发展至关重要，因为它包括进一步的培训 从我的导师，以及一个富有成效的合作努力的延续与另一位教员在 北卡罗来纳州大学。 了解调节组蛋白生物合成的机制对于了解组蛋白的生物合成是至关重要的。 与癌症相关的病理学。许多常见的化疗抗癌疗法旨在抑制肿瘤细胞的增殖。 DMA合成。抑制组蛋白的合成应该有一个同样有益的结果，因此， 对该途径的详细了解将增加能够治疗该疾病的药物的重复性。

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.