Computational Foundations for Comparative RNA Sequence and Structure

描述(由申请者提供)：RNA处于分子生物学重大范式转变的中心。我们之前对基因的观点和细胞如何从DNA中编码蛋白质的一般概念仍然普遍适用于细菌和古生菌。然而，在真核生物中，这种观点正在被这样的概念所取代，即有机体的复杂性与其基因组中编码的RNA的数量而不是蛋白质的数量成比例。这些RNA分子的功能性质与它们的高阶结构直接相关。因此，从序列中预测和鉴定该结构将为了解其功能细节提供基础。由于最近发现的一些RNA的结构和功能特性，如不同的微小RNA，参与了正常和异常细胞过程的调节，因此对RNA的研究有望有助于确定不同疾病的分子生物学，并为新的药物治疗提供基础。RNA序列和结构的比较分析在阐明RNA分子的整个结构以及鉴定和表征RNA的基本构件--结构基序和结构元件方面取得了非常成功的成果。这项建议的主要内容之一是建立了“比较RNA网(CRW)”网站，该网站为少数精选的RNA分子提供不同类型的比较信息的收集和分析。然而，基于本项目研究的最初一组RNA的序列数量的显著增加，以及现在正在识别的RNA数量的显著增加，我们正在开发一种新的计算基础，旨在建立可重复的协议，用于比较分析RNA序列和结构。目前的CRW网站将成为一个完全动态的网络服务，供一般科学界对他们自己的RNA进行比较分析，这得益于CRW网站收集的RNA序列和结构信息以及计算基础设施。公共卫生报告：基于RNA的功能重要性及其高阶结构，我们正在为RNA的比较分析开发一种新的计算基础。这一资源将使正在研究与细胞中许多不同的正常和异常过程相关的RNA的实验实验室受益，并可能直接影响新药疗法的开发。

DESCRIPTION (provided by applicant): RNA is in the center of a major paradigm shift in Molecular Biology. Our previous perspective of a gene and the general concept for how a cell codes for proteins from DNA is still generally true for Bacteria and Archaea. However, in Eukaryotes, this perspective is being replaced with the notion that the complexity of an organism scales with the amount of RNA, not Protein, that is coded for in its genome. The functional properties of these RNA molecules are directly associated with their higher-order structure. Thus the prediction and identification of this structure from sequence will provide the foundation to understand the details of their function. Since the structural and functional properties of some recently discovered RNAs, such as different micro RNAs, are involved in the regulation of normal and aberrant cellular processes, studies that focus on RNA are expected to help determine the molecular biology for different diseases, and provide the basis for new drug therapies. Comparative analysis of RNA sequences and structures have been very successful in the elucidation of the entire structure of an RNA molecule and in the identification and characterization of the basic building blocks of RNA - structural motifs and structural elements. One of the PIs of this proposal, has established the "Comparative RNA Web (CRW)" site that disseminates collections and analysis of different types of comparative information for a few select RNA molecules. However, based on the significant increase in the number of sequences for the initial set of RNAs studied in this project, and now the significant increase in the number of RNAs that are being identified, we are developing a novel computational foundation intended to establish repeatable protocols for the comparative analysis of RNA sequences and structures. The current CRW Site will become a fully dynamic web service for the general scientific community to perform comparative analysis on their own RNAs, benefiting from the collection of RNA sequence and structure information and the computational infrastructure at the CRW Site. PUBLIC HEALTH RELEVANDE: Based on the functional importance of RNA and its higher-order structure, we are developing a novel computational foundation for the comparative analysis of RNA. This resource will benefit experimental laboratories that are studying RNAs that are associated with many different normal and aberrant processes in the cell, and could directly influence the development of new drug therapies.