RNA Structurome in Post-Transcriptional Regulation

项目总结/摘要 我的研究计划侧重于开发和应用计算方法来确定 所有RNA转录物或转录组的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个步骤中起着关键作用，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 在转录组水平上的RNA结构（称为RNA结构组）。然而，人们所知甚少。 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 充分利用现有高通量数据集揭示RNA特征和功能的能力 结构体为了克服这些局限性，我正在建立一个独特的研究计划， 计算方法来表征，分析和解释RNA结构组的功能。来 在接下来的五年里，我的研究计划的目标是全面阐明RNA结构组， 精确预测RNA结构在RNA-蛋白质相互作用中的作用和RNA翻译的控制 转化成蛋白质。我们将开发一种新的分析框架，用于推断RNA结构组， 这是一个可用的高通量数据集，能够分析体内RNA结构。我们将使用这个框架 使用特定的细胞模型系统进行分析，包括表征特定RNA的多样性 在人类癌细胞系中调节RNA-蛋白质相互作用的结构， 在调节RNA和蛋白质之间的相互作用中的结构被证明是翻译所必需的 调节干细胞自我更新和早期胚胎发生。我们将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， 人类疾病的机制，包括神经系统疾病和癌症。成功发展 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， 功能，并揭示其对许多看似棘手的人类疾病的病因学的贡献。的 我的研究计划的总体愿景是建立我们与同事的合作网络，在 全国各地的学术医疗中心和医院，这将使我能够将我们的 计算方法（使用RNA结构组分析作为跳板），以提高我们的能力， 提供更准确的临床诊断和诊断，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.