Sequence and Structural Patterns in RNA

普渡大学被授予一个完整的信息学系统，用于识别保守的RNA结构拓扑，并在序列数据库中寻找类似拓扑的新实例。这将使RNA研究人员能够像DNA和蛋白质那样，经历同样的假设/搜索/假设-精炼循环。RNA在翻译、RNA剪接、基因调控和病毒感染等核心生化过程中发挥着核心作用。曾经被认为只是一个结构支架，现在人们意识到，RNA也可以作为一种酶本身或在核糖核蛋白复合体中发挥作用。然而，在理解RNA在细胞中扮演的角色方面的进展一直受到实验确定和计算分析RNA结构的困难的阻碍。基于识别保守结构的方法在推断DNA和蛋白质的功能特性方面一直是极其强大的。这是因为正是分子的功能使序列在进化过程中看起来是保守的。不幸的是，对RNA结构的类似分析是不可能的，因为保守作用在碱基对结构水平上，而不是在序列本身的水平上。由于许多其他生物学问题，如系统生物学、调节电路和某些类型的分子间结合，具有很强的图形成分，本项目开发的思想和软件将极大地促进生物学研究的其他领域。图挖掘也是计算机科学和其他学科中的一个重要学科，也可能从这项工作中受益。该项目期间的广泛影响活动包括对三名交叉培训的生物学和计算机科学博士生关于该项目各方面的研究。对高中的推广将包括关于RNA拓扑结构的模块。该项目的软件将公开提供：http://wiki.genomics.purdue.edu/index.php/Gribskov：：Main

"This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)."Purdue University is awarded a grant to implement a complete informatics system for identifying conserved RNA structure topologies, and for finding new examples of similar topologies in sequence databases. This will allow RNA researchers the same loop of hypothesis/search/hypothesis-refinement that has been so powerful for DNA and proteins.RNA plays a central role in core biochemical process such as translation, RNA-splicing, gene regulation, and viral infection. Once thought to be only a structural scaffold, it is now appreciated that RNA can also act as an enzyme on its own or in ribonucleoprotein complexes. However, advances in understanding the role that RNA plays in the cell has been hampered by the difficulty in experimentally determining and computationally analyzing RNA structures. Approaches based on identifying conserved structures have been extremely powerful in deducing functional properties of DNA and proteins. This is because it is the function of the molecule that makes the sequence appear conserved over evolutionary time. Unfortunately, a similar analysis has not been possible for RNA structures because the conservation acts at the level of the base-paired structure rather than that of sequence per se.Since many other biological problems, such as systems biology, regulatory circuits, and some kinds of intermolecular binding, have strong graphical components, the ideas and software developed in this project will significantly advance other areas of biological research. Graph mining is also an important subject in Computer Science and other disciplines, which may also benefit from this work.Broader impact activities during this project include the research of three PhD students, cross-trained in both Biology and Computer Science, on aspects of this project. Outreach to high schools will include modules on RNA topology structure. Software from this project will be made publically available: http://wiki.genomics.purdue.edu/index.php/Gribskov::Main