RNA Structurome in Post-Transcriptional Regulation

项目摘要/摘要 我的研究项目重点是开发和应用计算方法来确定 所有RNA转录本或转录组的RNA结构和功能之间的关系。RNA结构 在RNA合成和功能的几乎每一步都起着关键作用，并对生物学产生重大影响 过程和人类疾病。最近的高通量技术已经开始彻底改变解剖 转录组水平的RNA结构(称为RNA结构)。然而，人们对此知之甚少 RNA结构和功能之间的关系，很大程度上是因为目前的计算方法缺乏 能够充分利用可用的高通量数据集来揭示RNA的特征和功能 结构体系。为了克服这些限制，我正在建立一个独特的研究计划来开发小说 描述、分析和解释RNA结构功能的计算方法。超过了 未来五年，我的研究计划的目标是全面阐明RNA结构和 准确预测RNA结构在RNA-蛋白质相互作用中的作用及对RNA翻译的控制 转化为蛋白质。我们将开发一种新的分析框架来推断RNA结构，它整合了 可用的高通量数据集，并能够分析活体RNA结构。我们将使用此框架 用于使用特定细胞模型系统的分析，包括表征特定RNA的多样性 调节人类癌细胞中RNA-蛋白质相互作用的结构，并剖析RNA的作用 调节RNA和蛋白质相互作用的结构被证明是翻译所必需的 干细胞自我更新和早期胚胎发育的调控。我们将通过以下方式验证我们的计算预测 与具有相关专业知识的实验生物学家合作。在不久的将来，我们将应用我们的 通过与生物学家合作研究RNA结构在人类疾病中的作用的方法 人类疾病的机制，包括神经紊乱和癌症。成功地开发了 我们的方法将使我们和研究团体能够阐明从RNA结构到RNA的逻辑 并揭示了它们对许多看似难以治愈的人类疾病的病因学的贡献。这个 我的研究计划的总体愿景是与同事建立迅速发展的合作网络，网址为 全国各地的学术医疗中心和医院，未来将使我能够将我们的 计算方法(使用RNA结构分析作为跳板)，以提高我们的能力 提供更准确的临床诊断和预后，并开发新的、更有效的治疗方法。

PROJECT SUMMARY/ABSTRACT My research program focuses on development and application of computational approaches to determine the relationship between RNA structure and function for all RNA transcripts, or the transcriptome. RNA structure plays key roles in almost every step of RNA synthesis and function, and has significant impacts on biological processes and human diseases. Recent high-throughput technologies have begun to revolutionize dissection of RNA structures at the transcriptome level (termed RNA structuromes). However, little is known of the relationship between RNA structure and function, largely because current computational approaches lack the capacity to fully utilize the available high-throughput datasets to reveal the characteristics and functions of RNA structuromes. To overcome these limitations, I am building a unique research program to develop novel computational approaches to characterize, analyze and interpret the function of RNA structuromes. Over the next five years, the goals of my research program are to comprehensively elucidate RNA structuromes and precisely predict the functions of RNA structure in RNA-protein interactions and control of translation of RNA into proteins. We will develop a novel analytic framework for inferring RNA structuromes that integrates available high-throughput datasets and enables analysis of in vivo RNA structures. We will use this framework for analyses using specific cellular model systems, including characterizing the diversity of specific RNA structures that regulate RNA-protein interactions in a human cancer cell line, and dissecting the roles of RNA structure in modulating interactions between RNA and proteins shown to be essential for translational regulation of stem cell self-renewal and early embryogenesis. We will validate our computational predictions by collaborating with experimental biologists with relevant expertise. In the immediate future we will apply our approaches to study the roles of RNA structure in human diseases by collaborating with biologists working on the mechanisms of human diseases, including neurological disorders and cancer. Successful development of our approaches will allow us, and the research community, to elucidate the logic from RNA structure to RNA function and reveal their contributions to the etiology of numerous seemingly intractable human diseases. The overall vision of my research program is to build our burgeoning network of collaborations with colleagues at academic medical centers and hospitals across the nation that will, in the future, enable me to incorporate our computational approaches (using RNA structurome analysis as a springboard) to advance our capacity to render more accurate clinical diagnoses and prognoses, and develop novel, more effective therapies.