Structural Motifs in RNA

描述（申请人提供）：正确控制基因表达对生命至关重要。虽然在发现DNA序列和转录因子组合调节转录方面取得了重大进展，但对基因表达程序的后续步骤知之甚少。然而，现在已经清楚的是，在转录后，在pre-mRNA剪接、RNA转运、RNA定位、翻译和RNA衰变以及RNA结合蛋白（rbp）对RNA的协调中，都发生了实质性的调控和基因表达。此外，最近关于非编码rna （ncRNA）广泛转录以及这些rna参与关键生物过程（如发育和基因调控）的发现表明，我们刚刚开始探索的重要调控rna类别的存在。该项目的长期目标是开发能够在全基因组范围内对rna进行结构表征的工具。首先，我们将开发基于预测二级结构的计算方法来描述RNA中的功能基序。其次，我们将使用一系列RNA足迹技术和高分辨率平铺阵列技术开发高通量方法来绘制RNA的二级和三级结构。第三，我们将开发计算和实验方法来分配RNA基序的生物学功能并验证它们。这种新的实验和计算工具的集成管道将使研究人员能够以前所未有的速度和精度识别和解码基因组中的调控RNA元件。

DESCRIPTION (provided by applicant): Proper control of gene expression is essential for life. While substantial advances have been made in the discovery of DNA sequences and transcription factors that act combinatorial to regulate transcription, much less is known about later steps in the gene expression program. Nevertheless, it is now clear that substantial regulation and gene expression occurs post-transcriptional, in pre-mRNA splicing, RNA transport, RNA localization, translation, and RNA decay, and in the coordination of RNAs by RNA binding proteins (RBPs). Further, recent findings of widespread transcription of noncoding RNAs (ncRNA) and of the involvement of these RNAs in critical biological processes such as development and gene regulation suggest the existence of important classes of regulatory RNAs that we are just beginning to explore. The long term goal of this project is to develop tools that enable structural characterization of RNAs on a genome-wide scale. First, we will develop computational methods to delineate functional motifs in RNA based on predicted secondary structures. Second, we will develop high-throughput methodologies of mapping secondary and tertiary structures in RNA using a series of RNA footprinting techniques and high resolution tiling array technology. Third, we will develop computational and experimental methods to assign biological functions to RNA motifs and to validate them. This integrated pipeline of new experimental and computational tools will enable investigators to identify and decode regulatory RNA elements in the genome with unprecedented speed and precision. The control of gene expression lies at the heart of understanding fundamental biological processes, such as cell growth, differentiation, and death. A deep and comprehensive understanding of the gene expression program would help to reveal the mechanisms of many human diseases exhibiting faulty gene expression, and allow their diagnosis and intervention with newfound precision.