Supporting RNAstructure: Software for RNA Analysis

描述（申请人提供）：RNA在生物学的许多领域发挥着重要作用。在RNA水平上起作用的功能性RNA序列，即不作为mRNA编码区，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）。为了了解RNA的功能和利用RNA的力量，通过RNA干扰、治疗性RNA酶或RNA纳米结构，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。它已经被超过17000名不同的用户下载，可以在马修斯实验室的网站http://rna.urmc.rochester.edu上获得。它为RNA结构预测提供了最先进的算法，使用最新的RNA折叠热力学理解。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化寡核苷酸（DNA或RNA）退火对结构化RNA靶标的亲和力的方法。这些预测对于选择有效的小干扰RNA （siRNA）进行基因沉默具有重要意义。RNAstructure提供了友好的图形用户界面，使用c++（适用于Microsoft Windows）和JAVA（适用于Linux或Mac OS-X）。文本接口是为脚本或命令行使用而提供的。这些可以在Unix/Linux/Mac OS-X上编译，并为Windows提供了可执行文件。最后，还提供了一个共享的c++类库，供程序员在新程序中包含算法。建议扩展和维护rnas结构。为下一支助时期提出了四个正式目标。目标1是为rna结构提供一种新的向导模式，以指导用户分析它们的序列。目的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web接口提供所有rna结构组件。目标4是提供快速和准确的二级结构预测，包括假结，这是目前大多数算法无法预测的。

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.