Innovations in RNA Structure Prediction

RNA 结构预测的创新

基本信息

批准号：
8131933
负责人：
DAVID H. MATHEWS
金额：
$ 32.59万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-25 至 2012-11-30
项目状态：
已结题

项目摘要

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在细胞功能中起着许多重要作用。在生物学的中心教条中，RNA充当遗传信息的瞬态载体，也是读取代码的适配器分子。 RNA催化反应并用于转录后基因调控，发育和免疫力。 RNA在人类疾病中也起着作用，包括PRAEDER-WILLI和MYOTOCONS营养不良。理解和利用RNA的力量，例如使用RNAi，反义技术或使用治疗性核酶，需要了解这些RNA序列的结构。该提案的目标是（1）使用来自Dynalign的成对结构预测来确定RNA的比较序列分析，这是我们发现两个序列共有的二级结构的算法。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，但目前是劳动量大的，并且取决于科学家进行比较的技能。随着在不编码消息的情况下发现功能的新类别的非编码RNA（NCRNA）序列，新工具非常需要自动化二级结构的确定。（2）通过编写一个名为DynaFind的新软件包，进一步使用Dynalign进行NCRNA发现的方法。我们的NCRNA发现方法将粗略对齐的序列作为输入，并根据对齐中公共结构的折叠自由能的变化来识别假定的NCRNA。（3）使用DynaFind扫描人类和酵母基因组对新的NCRNA基因。我们将与我们的共同研究者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。改进的预测RNA结构的工具将有助于发现RNA或靶RNA的治疗剂。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。