Identification, Discovery, and Public Archiving of RNA Structural Motifs

RNA 结构基序的鉴定、发现和公共存档

• 批准号: 9897534
• 负责人: Shaojie Zhang
• 金额: $ 17.46万
• 依托单位: UNIVERSITY OF CENTRAL FLORIDA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9897534
• 关键词: 3-Dimensional; Achievement; Algorithms; Archives; Back; Base Pairing; Binding Proteins; Biological; Biological Process; Biomedical Research; Catalysis; Characteristics; Classification; Communities; Computing Methodologies; Consensus; Data Sources; Databases; Development; Disease; Dyskeratosis Congenita; Family; Family member; Foundations; Functional disorder; Gene Expression Regulation; Goals; Grant; Knowledge; Lead; Life; Link; Methods; Modeling; Pattern; Physiological; Play; Positioning Attribute; Prader-Willi Syndrome; Progress Reports; Property; RNA; RNA Splicing; Recurrence; Research; Resources; Role; Services; Solid; Statistical Models; Structure; Time; Untranslated RNA; Variant; Work; base; comparative; computational suite; design; experimental study; improved; large scale data; loss of function; novel; novel strategies; programs; three dimensional structure; tool; treatment strategy; user-friendly; web server

Project Summary The non-coding RNAs (ncRNAs) play many functional roles in biological processes, such as catalysis, gene expression regulation, and RNA splicing. The various roles played by ncRNAs are determined by their charac- teristic 3D structures. RNA structural motifs are recurrent structural components in ncRNAs. The RNA structural motifs have conserved structures, and therefore, are expected to have similar biological or structural functions. For instance, the kink-turn motif is found in different kinds of ncRNAs and most of them are responsible for protein binding activities. Any alteration of the motif structures has the potential to result in loss-of-function of the RNA structural motif, and in some cases may cause severe diseases. Therefore, the study of RNA structural motif will help us to elucidate the mechanisms of many diseases and lead to the development of novel treatment strategies. Driven by the requirement of biomedical research, many computational methods have been proposed to detect instances of known motifs or to discover novel families. Recently, the rapidly increasing number of resolved RNA 3D structures urges the development of new tools to make use of the huge amount of resources in PDB. In our opinion, the large-scale dataset will support two new approaches for RNA structural motif analysis: generating profiles to represent motif families and to search for new instances, and identifying the structural and functional relationship among different motifs. In this proposal, we aim at devising a suite of computational methods based on these two ideas. First, we will build 3D position-specific scoring matrixes (PSSMs) as profiles to represent the base-pairing interactions in the discovered RNA structural motif families and develop profiled-based RNA structural motif search tools. Considering the fact that all the existing RNA structural motif searching programs rely on consensus, the introduction of profiles will create a great opportunity to improve the search accuracy. In the mean time, the new profile model will provide us a formal method to describe motif families, which is very critical for the understanding of the relationship between RNA 3D structures and their functionalities. Second, we will distinguish the structural features of motif family members to identify subfamilies, and study the potential re- lationship among families to recognize clans and modules. The RNA structural motifs from different families may share similar structural features, and they can also interact with each other to perform certain specific functions. As far as we know, there is no existing research about the mentioned relationships among RNA structural motifs. Now, the de novo discovery of RNA motif families from the clustering results grants us a solid foundation for further research at both intra- and inter-family levels. With the achievement of these two goals, we also propose to build a new RNA structural motif database to incorporate all the newly discovered knowledge in this project. The tools will also be implemented as user-friendly web servers and integrated with the database to provide a well-rounded service. We expect that the proposed work will lead to better understanding of the RNA structural motifs, and significantly promote biomedical research.

项目概要 非编码RNA（ncRNA）在生物过程中发挥着许多功能作用，例如催化、基因 表达调控和RNA剪接。 ncRNA 发挥的各种作用是由它们的特性决定的： 立体 3D 结构。 RNA 结构基序是 ncRNA 中重复出现的结构成分。 RNA结构 基序具有保守的结构，因此预计具有相似的生物学或结构功能。 例如，kink-turn 基序存在于不同种类的 ncRNA 中，其中大多数负责蛋白质 绑定活动。基序结构的任何改变都有可能导致 RNA 功能丧失 结构基序，在某些情况下可能导致严重的疾病。因此，RNA结构基序的研究将 帮助我们阐明许多疾病的机制并开发新的治疗策略。 在生物医学研究的需求驱动下，人们提出了许多计算方法来检测 已知主题的实例或发现新的家族。最近，解析RNA的数量迅速增加 3D结构促使新工具的开发，以利用PDB中的大量资源。在我们的 认为，大规模数据集将支持两种新的 RNA 结构基序分析方法：生成 配置文件来表示主题家族并搜索新实例，并识别结构和功能 不同主题之间的关系。在这个提案中，我们的目标是设计一套基于计算方法 就这两个想法。首先，我们将构建 3D 特定位置评分矩阵 (PSSM) 作为配置文件来表示 发现的 RNA 结构基序家族中的碱基配对相互作用并开发基于图谱的 RNA 结构主题搜索工具。考虑到所有现有的 RNA 结构基序搜索程序 依靠共识，配置文件的引入将为提高搜索准确性创造一个很好的机会。在 同时，新的轮廓模型将为我们提供一种描述主题家族的正式方法，这是非常有用的 对于理解 RNA 3D 结构及其功能之间的关系至关重要。第二，我们 将区分基序家族成员的结构特征以识别亚家族，并研究潜在的重新 家庭之间的关系以识别氏族和模块。来自不同家族的RNA结构基序可能 它们具有相似的结构特征，并且它们还可以相互作用以执行某些特定功能。 据我们所知，目前还没有关于RNA结构基序之间上述关系的研究。 现在，从聚类结果中重新发现 RNA 基序家族为我们提供了坚实的基础 在家庭内部和家庭间层面进行进一步的研究。随着这两个目标的实现，我们还提出 建立一个新的RNA结构基序数据库，以纳入该项目中所有新发现的知识。 这些工具还将作为用户友好的网络服务器来实现，并与数据库集成以提供 周到的服务。我们期望所提出的工作将有助于更好地理解 RNA 结构 主题，并显着促进生物医学研究。