Supporting RNAstructure: Software for RNA Analysis

描述（由申请人提供）：RNA在生物学的许多领域中起着重要作用。在RNA水平工作的功能性RNA序列，即不作为mRNA编码区，被称为非编码RNA（ncRNA）。ncRNA序列具有不同的作用，从序列识别（如RNA干扰中的杂交）到催化反应（如核糖体RNA的肽键形成）。为了了解RNA的功能，并利用RNA的力量，RNA干扰，治疗性RNA酶或RNA纳米结构，需要了解RNA结构。 RNAstructure是一个RNA二级结构预测和分析软件包。它已经被超过17，000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。它提供了最先进的算法，RNA结构预测使用最新的理解RNA折叠热力学。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，它提供了预测结构化寡核苷酸（DNA或RNA）退火至结构化RNA靶标的亲和力的方法。这些预测对于选择用于基因沉默的有效小干扰RNA（siRNA）是重要的。 RNAstructure提供了用户友好的图形用户界面，用于Microsoft Windows的C++和用于Linux或Mac OS-X的JAVA。提供文本接口供脚本或命令行使用。这些可以在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。 该建议是为了延长和维持RNA结构。为下一个支助期提出了四个正式目标。目的1是为RNAstructure提供一种新的向导模式，以指导用户分析其序列。目的2是更新最近邻参数预测构象稳定性使用最新的实验数据。目标3是通过Web接口提供所有RNAstructure组件。目的4是提供快速和准确的预测二级结构，包括伪结，这是目前大多数算法预测。 公共卫生相关性：该提案与公共卫生直接相关。我们提供用于预测，理解和靶向RNA结构的软件工具。这些可以应用于理解传染病的生物学，因为一些病毒，包括流感和艾滋病毒，是RNA病毒。此外，它们还可以用于设计新的治疗方法，例如都靶向RNA的反义寡核苷酸或小干扰RNA。这种RNA靶向疗法可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.