RNA Structure and Dynamics In Vivo

智慧的MeritRNA在生命系统中充当信息的中央管道。RNA分子编码遗传信息，也是细胞中催化和调节机制的关键组件。在一个例子中，核糖体是一台微调的机器，它将信使RNA中编码的信息翻译成蛋白质。核糖体包含两个大的RNA分子和许多蛋白质，这个基本的细胞机器的功能是由其蛋白质和RNA成分之间复杂的结构和动态相互作用所支配的。在第二个例子中，RNA病毒可能是我们生物圈中最成功的复制实体。RNA病毒复制的几乎每一步都涉及到它们的RNA基因组与病毒和细胞蛋白之间高度进化的相互作用。在理解核糖体和RNA病毒方面，基于遗传、生化和高分辨结构的方法已经取得了非凡的进展。然而，细胞环境对RNA功能的影响仍然知之甚少。该项目的总体愿景是使SHAPE(选择性2‘-羟基酰化分析)RNA结构分析技术成为分析细胞和病毒颗粒内部RNA结构的强大工具。该项目五年的具体研究目标是使用SHAPE在健康、生长的细胞中建立蛋白质合成过程中的大肠杆菌核糖体RNA的结构，并确定二十面体正链病毒的RNA基因组结构，以揭示病毒RNA基因组包装的广泛原理。Broader Impact准确高效地分析细胞内RNA结构的技术具有改变生物科学许多领域的潜力。当完全开发时，SHAPE技术将允许在高度纯化的系统中合成从高分辨率结构方法获得的信息，并进行细胞功能和适合性研究。Shape技术也足够成熟，可以作为一个完全由本科生驱动的研究项目--本科生转录组项目(UTP)的基础。本科生将独立开展病毒RNA基因组包装的研究。UTP旨在帮助本科生发掘独立创造力的潜力，激发他们对科学的热情，促进研究生的高水平指导，并成为研究型大学本科生参与的典范。

Intellectual MeritRNA functions as the central conduit for information in living systems. RNA molecules encode genetic information and also serve as critical component in the catalytic and regulatory machinery in cells. In one example, the ribosome is a finely tuned machine that translates the information coded in messenger RNA into proteins. The ribosome contains two large RNA molecules and many proteins and the function of this essential cellular machine is governed by complex structural and dynamic interactions among its protein and RNA components. In a second example, RNA viruses represent perhaps the most successful replicating entities in our biosphere. Almost every step in RNA virus replication involves highly evolved interactions between their RNA genome and viral and cellular proteins. Extraordinary progress in understanding the ribosome and RNA viruses has been made based on genetic, biochemical, and high-resolution structure approaches. However, the impact of the cellular environment on RNA function remains poorly understood. The overarching vision of this project is to make the SHAPE (selective 2'-hydroxyl acylation analyzed by primer extension) RNA structure analysis technology a robust tool for analysis of RNA structure in cells and inside viral particles. The specific research goals over five years of the project are to use SHAPE to establish the structure of E. coli ribosomal RNA during protein synthesis in healthy, growing cells and to determine the RNA genome structure of an icosahedral plus-strand virus to reveal broad principles of viral RNA genome packaging.Broader Impact Accurate and efficient technology for analyzing RNA structure inside cells has the potential to transform many fields in the biological sciences. When fully developed, SHAPE technology will allow synthesis of information obtained from high-resolution structural approaches in highly purified systems with function and fitness studies in cells. SHAPE technology is also sufficiently mature to serve as the basis for a completely undergraduate-driven research endeavor, the Undergraduate Transcriptome Project (the UTP). Undergraduates will, independently, carry out the research on viral RNA genome packaging. The UTP is designed to help undergraduates explore their potential for independent creativity, to fuel their passion for science, to promote high-level mentoring by graduate students, and to be a model for engaging undergraduates in a research university.