Contribution of Dynamic Processes to RNA-Protein Complex Formation

该奖项是根据2009年美国复苏和再投资法案(公法111-5)资助的。在这项研究中，将调查动力学在RRM-RNA复合体关联中的复杂作用。RNA识别基序(RRM)是一种普遍存在的RNA结合蛋白，存在于所有生物体中，参与基因表达的所有步骤。因此，了解RRM-RNA结合是完整描述基因表达的基础。蛋白质和RNA结合时的构象变化是RNA-蛋白质识别中的普遍现象，包括RNA-RRM识别。该项目的具体目标是开发一种通用的方法，使用分子动力学模拟支持的时间分辨荧光方法来研究RRM-RNA复合体中的动态过程。这种方法随后将被用于研究涉及RRMS的更复杂的生物系统。拟议研究的一个重要组成部分是调查两种不同RRM蛋白中一系列修饰的蛋白质和RNA靶标的动力学，以确定蛋白质和RNA序列对结合所涉及的动态过程的贡献，并确定RRM-RNA识别的一般原理。广泛影响：这项研究将对三类学生的教育产生更广泛的影响：研究生、越南的化学学生和高中化学教师。首先，直接参与拟议工作的研究生和本科生将从该项目的跨学科和协作性质中受益匪浅。拟议研究的影响将超越这些学生，因为它将是实验室更大的综合研究计划的一部分，也将对合作实验室的学生教育做出积极贡献。其次，国际和平研究所将参与越南河内大学的一个项目。该项目包括来自越南的客座教授在伊利诺伊大学参加国际学生联合会授课的课程，国际学生联合会前往越南教授有机化学，以及越南学生在夏季在国际学生联合会的实验室工作。第三，国际和平研究所正在参与一项由美国国家科学基金会资助的名为“通过计算科学提高化学素养研究所”的数学与科学伙伴关系项目。该计划在伊利诺伊州教师和农村高中教师之间建立了伙伴关系，以广泛提高伊利诺伊州教师和学生对化学的理解。PI在一个为期两周的暑期学院任教，高中教师在那里参加全天的研讨会。PI每周都会使用公告牌式的交流系统为一组7名高中教师提供指导。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).In this research, the complex role of dynamics in the association of RRM-RNA complexes will be investigated. The RNA recognition motif (RRM) is a ubiquitous RNA binding protein that is found in all organisms and is involved in all steps of gene expression. Thus, an understanding of RRM-RNA binding is fundamental to a complete description of gene expression. Conformational changes of both protein and RNA upon binding are a general phenomenon in RNA-protein recognition, including RNA-RRM recognition. The specific goals of this project are to develop a general approach for investigating dynamic processes in RRM-RNA complexes using time-resolved fluorescence methods supported by molecular dynamics simulations. This approach will then be used to investigate more complex biological systems involving RRMs. An essential component of the proposed studies is the investigation of the dynamics of a series of modified proteins and RNA targets in two different RRM proteins in order to determine the contribution of protein and RNA sequence to dynamic processes involved in binding and identify general principles of RRM-RNA recognition.Broader Impacts: This research will have broader impacts in the education of three types of students: research students, chemistry students in Vietnam, and high school chemistry teachers. First, the graduate and undergraduate students directly involved in the proposed work will benefit greatly from the interdisciplinary and collaborative nature of the project. The impact of the proposed research will extend beyond these students, as it will be part of a larger comprehensive research program in the laboratory and also will contribute positively to students' education in the collaborating laboratories. Second, the PI will be involved in a project with Hanoi University in Vietnam. This program involves visiting professors from Vietnam attending classes taught by the PI at the University of Illinois, travel of the PI to Vietnam to teach organic chemistry, and Vietnamese students working in the PI's laboratory during summers. Third, the PI is participating in an NSF-funded Math and Science Partnership project entitled "Institute for Chemistry Literacy through Computational Science". This program creates a partnership between Illinois faculty and rural high school teachers to broadly improve teachers' and students' understanding of chemistry across the state of Illinois. The PI teaches in a 2-week Summer Institute, where the high school teachers participate in full-day workshops. The PI is involved weekly in serving as a mentor to a group of 7 high school teachers using a bulletin board-type communication system.