Supporting RNAstructure: Software for RNA Analysis

描述(申请人提供)：RNA在生物学的许多领域中扮演着重要的角色。在RNA水平上工作的功能RNA序列，即不作为mRNA编码区，被称为非编码RNA(NcRNA)。NcRNA序列具有多种功能，从序列识别(如RNA干扰中的杂交)到催化反应(如核糖体RNA形成肽键)。要了解RNA的功能并利用RNA干扰、治疗性RNA酶或RNA纳米结构来利用RNA的力量，需要了解RNA的结构。RNAStructure是一个用于RNA二级结构预测和分析的软件包。它已被17,000多个不同的用户下载，并可在马修斯实验室网站http://rna.urmc.rochester.edu.上获得它利用对RNA折叠热力学的最新理解，为RNA结构预测提供了最先进的算法。它还提供了寻找两个序列共享的最佳二级结构的算法，平均而言，这比预测单个序列的结构要准确得多。此外，它还提供了预测结构寡核苷酸(DNA或RNA)退火对结构RNA靶标的亲和力的方法。这些预测对于筛选有效的小干扰RNA(SiRNA)用于基因沉默具有重要意义。RNAStructure以C++(适用于Microsoft Windows)和Java(适用于Linux或Mac OS-X)提供了用户友好的图形用户界面。提供文本界面以供脚本或命令行使用。这些代码可以在Unix/Linux/Mac OS-X上编译，并为Windows提供可执行文件。最后，一个共享的C++类库可供程序员在新程序中包含算法。该提案是为了扩展和维护RNA结构。提出了下一个支助期的四个正式目标。目的1是为RNA结构提供一种新的向导模式，以指导用户完成序列分析(S)。目标2是利用最新的实验数据更新预测构象稳定性的最近邻参数。目标3是通过网络接口提供所有的RNA结构组件。目标4是提供对包含伪结点的二级结构的快速和准确的预测，目前大多数算法都没有预测到伪结点。 公共卫生相关性：该提案具有直接的公共卫生相关性。我们提供用于预测、理解和定位RNA结构的软件工具。这些可以用来理解传染病的生物学，因为包括流感和艾滋病毒在内的一些病毒是RNA病毒。此外，它们还可用于设计新的治疗药物，如反义寡核苷酸或小干扰RNA，两者都针对RNA。这种RNA靶向疗法可以用于癌症或遗传性疾病等疾病。

DESCRIPTION (provided by applicant): RNA plays important roles in many areas of Biology. Functional RNA sequences that work at the level of RNA, i.e. not as an mRNA coding region, are called non-coding RNA (ncRNA). ncRNA sequences serve diverse roles from sequence recognition, such as hybridization in RNA interference, to catalyzing reactions, such as peptide bond formation by ribosomal RNA. To understand RNA function and to harness the power of RNA, with RNA interference, therapeutic RNA enzymes, or RNA nanostructures, an understanding of RNA structure is required. RNAstructure is a software package for RNA secondary structure prediction and analysis. It has been downloaded by over 17,000 different users and is available at the Mathews lab website http://rna.urmc.rochester.edu. It provides state-of-the-art algorithms for RNA structure prediction using the most current understanding of RNA folding thermodynamics. It also provides algorithms for finding the optimal secondary structure shared by two sequences, which is, on average, much more accurate than predicting a structure for a single sequence. Furthermore, it provides methods to predict the affinity of structured oligonucleotides (DNA or RNA) annealing to a structured RNA target. These predictions are important for the selection of effective small interfering RNA (siRNA) for gene silencing. RNAstructure is provided with user-friendly graphical user interfaces in C++ for Microsoft Windows and in JAVA for Linux or Mac OS-X. Text interfaces are provided for scripting or command line use. These can be compiled on Unix/Linux/Mac OS-X and executables are provided for Windows. Finally, a shared C++ class library is available for programmers to include algorithms in new programs. The proposal is to extend and maintain RNAstructure. Four formal aims are proposed for the next period of support. Aim 1 is to provide a new wizard mode for RNAstructure to guide users through the analysis of their sequence(s). Aim 2 is to update the nearest neighbor parameters for predicting conformational stability using the most recent experimental data. Aim 3 is to provide all the RNAstructure components via web interfaces. Aim 4 is to provide fast and accurate prediction of secondary structures that include pseudoknots, which are currently not predicted by most algorithms. PUBLIC HEALTH RELEVANCE: This proposal has direct public health relevance. We provide software tools for predicting, understanding, and targeting RNA structure. These can be applied to understanding the biology of infectious diseases because some viruses, including influenza and HIV, are RNA viruses. Furthermore, they can be used to design novel therapeutics, such as antisense oligonucleotides or small interfering RNA that both target RNA. This RNA-targeting therapeutics could be used for diseases such as cancer or inherited diseases.