RUI: Examining Non-Canonical Interactions in Small RNA Motifs

智力优势：RNA分子在基因表达的各个方面以及许多其他细胞过程中发挥着重要作用。在细胞内，RNA分子形成不同的结构，与DNA、蛋白质、其他RNA相互作用，并与各种代谢物相互作用，实现这些功能。RNA分子含有各种重复的结构特征或基序。本项目旨在增加对重复RNA基序内结合细节的理解，并阐明RNA结构形成的规则。科罗拉多学院的本科生将使用热力学方法测量小RNA结构的稳定性，包括热变性和等温量热法。然后，RNA的特定区域将被修饰，修改前后的RNA稳定性将被比较，以确定每个结构基序的键的关键贡献者。更好地理解结构形成的一般规则将提高我们从基因组数据库中获得更多信息的能力，预测细胞中由RNA形成的结构，并阐明它们的功能和作用机制。反复出现的RNA结构的详细热力学参数指导和稳定了RNA在转录时的折叠，这将提高我们对RNA折叠的理解，因为这些结构可能是形成高阶结构的成核位置。更广泛的影响：这项工作的更广泛的影响包括提高对RNA结构基序的知识的科学影响，以及在课堂内外招募和培训本科生使用当前的研究方法。生物化学课程的实验室正在进行改造，以便向课堂上的学生介绍研究方法。在核酸生物化学课程中，学生将设计一个基于RNA的项目，并应用他们的热力学知识来理解RNA的结构。该项目将通过将热力学和RNA的结构和功能引入到RNA研究中来加强他们的理解。本科生将被提供从他们的入门课开始进行研究的选项。最多八名本科生将在研究实验室工作，并参与开发和测试关于小RNA结构和功能的假设。生物化学班的女性和少数族裔学生将优先在实验室进行研究。此外，本科生将有机会参加朗费罗和奥杜邦小学的外展工作。小学生将通过检验关于溶解度和密度等概念的假设来学习科学的基本原理。学生将利用他们的科学知识向公众提供有关艾滋病毒生命周期及其治疗等主题的RNA信息，从而为社会做出积极贡献；这反过来又使科学与他们的生活相关。面向社区的科学推广项目是专门为提高公众的科学素养而设计的。与科罗拉多大学科罗拉多分校共享设备和专业知识将在当地搭建桥梁，并将使所有相关各方受益。Pine Creek高中的高中生和老师也将在暑期参与RNA研究。Pine Creek高中的生物课程将引入定量方法。

Intellectual Merit:RNA molecules play important roles in all aspects of gene expression as well as many other cellular processes. Inside the cell, RNA molecules form distinct structures to interact with DNA, proteins, other RNAs and with various metabolites to carry out these functions. RNA molecules contain various recurrent structural features or motifs. This project aims to increase understanding of the details of bonding within recurrent RNA motifs and to elucidate rules for RNA structure formation. Colorado College undergraduates will measure the stabilities of small RNA structures using thermodynamic methods, including thermal denaturation and isothermal calorimetry. Particular regions of RNA will then be modified, and RNA stabilities before and after the modification will be compared to identify key contributors to bonding for each structural motif. Improved understanding of the general rules for structure formation will improve our ability to get greater information from the genome databases, to predict the structures formed by RNA in the cell and to elucidate their functions and mechanisms of action. Detailed thermodynamic parameters for recurrent RNA structures that guide and stabilize the folding of RNA as it is transcribed will improve our understanding of RNA folding, as these structures may serve as nucleation sites for the formation of higher-order structures. Broader Impact:Broader impacts of this work include the scientific impact of improved knowledge of RNA structural motifs and recruitment and training of undergraduates in current research methods both inside and outside of the classroom. The laboratories in biochemistry courses are being modified to introduce research methodology to the students in the classroom. In nucleic acids biochemistry course, students will design an RNA-based project and apply their thermodynamic knowledge to understanding RNA structures. This project will strengthen their understanding of thermodynamics and RNA structure and function along introducing them to RNA research. Undergraduate students will be presented with an option to do research starting in their introductory classes. Up to eight undergraduate students will work in the research laboratory and participate in developing and testing hypotheses on small RNA structure and function. Women and minority students from biochemistry classes will be given priority to do research in the laboratory. In addition, undergraduate students will be provided opportunities to participate in outreach work with Longfellow and Audubon Elementary Schools. Elementary school students will learn the basic principles of science by testing hypothesis on concepts such as solubility and density. Students will make a positive contribution to the society by using their scientific knowledge to provide information about RNA to the general public on topics such as HIV's life cycle and its treatment; this in turn makes science relevant to their lives. The science outreach projects to the community are specifically designed to raise the scientific literacy of the general public. Sharing of equipment and expertise with University of Colorado, Colorado Springs will build bridges locally and will benefit all involved. High school students and teachers from Pine Creek High School will also participate in RNA research during the summer. Quantitative methods will be introduced into biology courses at Pine Creek High School.