Innovations in RNA Structure Prediction

RNA 结构预测的创新

• 批准号: 7383165
• 负责人: DAVID H. MATHEWS
• 金额: $ 34万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-25 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7383165
• 关键词: Algorithms; Antisense Technology; Base Pairing; Biology; Catalytic RNA; Cell physiology; Class; Code; Computer software; Development; Evolution; Free Energy; Functional RNA; Fungal Genome; Gene Expression Regulation; Genes; Genetic Carriers; Genome; Goals; Gold; Health; Human; Human Genome; Immunity; In Vitro; Methods; Myotonic Dystrophy; Object Attachment; Peptides; Play; RNA; RNA Interference; RNA Sequence Analysis; RNA Sequences; RNA Splicing; Range; Reaction; Reading; Research; Research Personnel; Role; Role playing therapy; Scanning; Scientist; Sequence Analysis; Sequence Homologs; Standards of Weights and Measures; Structure; Testing; Therapeutic; Work; Writing; base; comparative; genome sequencing; human disease; improved; innovation; novel; programs; skills; tool

DESCRIPTION (provided by applicant): RNA plays many important roles in cellular function. In the Central Dogma of Biology, RNA serves as a transient carrier of genetic information and as the adapter molecule that reads the code. RNA catalyzes reactions and serves in post-transcriptional gene regulation, development, and immunity. RNA also plays roles in human disease, including Praeder-Willi and myotonic dystrophy. Understanding and harnessing the power of RNA, e.g. with RNAi, antisense technology, or with therapeutic ribozymes, requires an understanding of the structures of these RNA sequences. The goals of this proposal are to (1) Automate comparative sequence analysis of RNA to determine RNA secondary structure using pairwise structure predictions from Dynalign, our algorithm that finds the secondary structure common to two sequences. Comparative sequence analysis is the gold standard for determining RNA secondary structure in the absence of a crystal structure, but is currently labor intensive and dependent on the skill of the scientist doing the comparison. With the discovery of new classes of non-coding RNA (ncRNA) sequences that function without coding message, there is a significant need for new tools to automate the determination of secondary structure. (2) Further develop our method using Dynalign for ncRNA discovery by writing a new software package called Dynafind. Our method for ncRNA discovery takes crudely aligned sequence as input and identifies putative ncRNAs on the basis of the folding free energy change of the common structure in the alignment. (3) Scan the human and yeast genomes for novel ncRNA genes using Dynafind. We will collaborate with our co-investigators, Dr. Eric Phizicky and Dr. Todd Lowe, to test the function of putative ncRNAs that we identify. This work has broad implications for human health. Improved tools for predicting RNA structure will help in the discovery of therapeutics that are either RNA or target RNA. The discovery of novel ncRNA in the human genome will contribute to our understanding of development and cellular physiology.

描述（由申请人提供）：RNA 在细胞功能中发挥许多重要作用。在生物学的中心法则中，RNA 充当遗传信息的瞬时载体和读取代码的衔接分子。 RNA 催化反应并参与转录后基因调控、发育和免疫。 RNA还在人类疾病中发挥着重要作用，包括普瑞德-威利病和强直性肌营养不良。理解并利用 RNA 的力量，例如使用 RNAi、反义技术或治疗性核酶，需要了解这些 RNA 序列的结构。该提案的目标是 (1) 自动进行 RNA 比较序列分析，以使用 Dynalign 的成对结构预测来确定 RNA 二级结构，Dynalign 是我们的算法，可找到两个序列共有的二级结构。比较序列分析是在没有晶体结构的情况下确定 RNA 二级结构的黄金标准，但目前是劳动密集型的，并且依赖于进行比较的科学家的技能。随着无需编码信息即可发挥作用的新型非编码 RNA (ncRNA) 序列的发现，迫切需要新工具来自动确定二级结构。 (2) 通过编写一个名为 Dynafind 的新软件包，进一步开发我们使用 Dynalign 进行 ncRNA 发现的方法。我们的 ncRNA 发现方法将粗略比对的序列作为输入，并根据比对中常见结构的折叠自由能变化来识别假定的 ncRNA。 (3) 使用 Dynafind 扫描人类和酵母基因组中的新 ncRNA 基因。我们将与我们的共同研究人员 Eric Phizicky 博士和 Todd Lowe 博士合作，测试我们确定的假定 ncRNA 的功能。这项工作对人类健康具有广泛的影响。预测 RNA 结构的改进工具将有助于发现 RNA 或靶 RNA 疗法。人类基因组中新型 ncRNA 的发现将有助于我们对发育和细胞生理学的理解。