Structural Motifs in RNA

RNA 中的结构基序

• 批准号: 9600971
• 负责人: John Perona
• 金额: $ 45万
• 依托单位: University of California-Santa Barbara
• 依托单位国家: 美国
• 项目类别: Continuing grant
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-07-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9600971&HistoricalAwards=false
• 关键词: Structural; Motifs; RNA

9600971 Perona Recent discoveries of new catalytic functions of RNA have greatly heightened awareness of the pivotal role of this molecule in living organisms. A full appreciation of the biological function of RNA must include a thorough description of how its three-dimensional structure is organized, but to date very few atomic-level descriptions of RNA molecules are available. Our previous work on crystallization and structure determination of the glutaminyl-tRNA synthetase-tRNAGIn complex provides a unique vehicle to rapidly determine the structures of new domains of RNA, the focus of the proposed project. The pre-existing crystal lattice of this large protein-RNA complex will be exploited by inserting new domains of RNA into specific positions of the tRNA, so that the new material is accomodated in the solvent interstices of the crystal. In-vitro selection methods are employed to obtain novel hybrid RNA molecules which fold correctly and retain biological activity. These new RNAs are chosen for their potential to teach us the underlying rules of three-dimensional folding and for their present-day biological significance. A rapid increase in new RNA structures will provide fundamental insight into RNA-based cellular processes and may have further implications to defining a new class of targets for structure-based drug design. The establishment of a laboratory engaged in Macromolecular Crystallography has been a long-awaited development at UCSB. Consequently, a significant activity in the next five years will be the education of students as well as other faculty members in related fields. Because a joint appointment is held in Chemistry and in an Interdepartmental Biochemistry and Molecular Biology Program (BMB), the range of interactions will be especially broad. A new graduate course in crystallography will be developed, and an existing course in Physical Biochemistry has already been extensively revised. State of the art data collection and computer graphics facilities enhance the educat ional opportunities by providing hands-on experience in the most important techniques. The arrival of crystallography also marks the onset of a long-term growth phase in Biochemistry and Biophysics at UCSB. Thus, there will be substantial participation in several new undergraduate curricula related to Structural Biology: a new B.S. degree in Biochemistry to be awarded by the Chemistry department, and an interdisciplinary program in Pharmacological Sciences. The University also possesses strong commitments to supporting undergraduate research opportunities, as manifested by programs funded by the Howard Hughes Medical Institute and the Materials Research Laboratory. Direct mentoring of undergraduates in the laboratory will be an important aspect of the educational program. Collaborative projects inside the University, as well as with senior scientists at other institutions, enhance the educational opportunities for students in the laboratory. %%% The fundamental building-block molecules in all living cells are DNA, RNA and protein. DNA encodes the genetic information within its nucleotide sequence, but for the cell to function this information must first be copied into a similar molecule, RNA, and then translated into protein. Until recently it was thought that proteins were the only molecules in cells capable of carrying out the necessary chemical and mechanical life processes. However, new discoveries have shown that RNA has a similar capability. We seek to understand how RNA can perform complex functions historically attributed only to protein. To do this requires visualization of RNA structure in three dimensions, a feat accomplished by inducing very pure samples of RNA to form well-ordered crystals which are analyzed by Xray diffraction. In our laboratory we are developing a new experimental system to grow crystals of RNA molecules bound to protein rather than in the usual unbound state. This system has the potential to allow us to rapidly determine many new RNA structures. We expect that the structures will provide us with fundamental insight into the functional roles of RNA in essential cellular processes. ***

9600971 Perona最近发现的新的催化功能的RNA大大提高了认识的关键作用，这种分子在活的有机体。要全面了解RNA的生物学功能，必须彻底描述其三维结构是如何组织的，但迄今为止，对RNA分子的原子级描述很少。我们以前的工作结晶和结构测定的dexaminyl-tRNA合成酶-tRNAGln复合物提供了一个独特的工具，以快速确定新的结构域的RNA，重点提出的项目。这种大的蛋白质-RNA复合物的预先存在的晶格将通过将新的RNA结构域插入tRNA的特定位置来利用，使得新材料容纳在晶体的溶剂间隙中。采用体外选择方法来获得正确折叠并保留生物活性的新型杂合RNA分子。选择这些新的RNA是因为它们有可能教会我们三维折叠的基本规则，以及它们在当今的生物学意义。新RNA结构的快速增加将为基于RNA的细胞过程提供基本的见解，并可能对定义一类新的基于结构的药物设计的靶点产生进一步的影响。 建立一个从事高分子晶体学的实验室是UCSB期待已久的发展。因此，今后五年的一项重要活动将是对学生和相关领域的其他教员进行教育。因为联合任命是在化学和跨部门的生物化学和分子生物学计划（BMB）举行，互动的范围将特别广泛。一个新的晶体学研究生课程将被开发，现有的物理生物化学课程已经被广泛修订。最先进的数据收集和计算机图形设施通过提供最重要技术的实践经验来提高教育机会。晶体学的到来也标志着UCSB生物化学和生物物理学长期增长阶段的开始。因此，将有大量参与与结构生物学相关的几个新的本科课程：一个新的学士学位。生物化学学位将由化学系授予，以及药理学科学的跨学科课程。该大学还拥有强大的承诺，以支持本科生的研究机会，如由霍华德休斯医学研究所和材料研究实验室资助的计划所示。在实验室直接指导本科生将是教育计划的一个重要方面。大学内部的合作项目，以及与其他机构的高级科学家，提高了学生在实验室的教育机会。 所有活细胞的基本组成部分是DNA、RNA和蛋白质。DNA在其核苷酸序列中编码遗传信息，但为了使细胞发挥功能，这些信息必须首先复制到类似的分子RNA中，然后翻译成蛋白质。直到最近，人们还认为蛋白质是细胞中唯一能够进行必要的化学和机械生命过程的分子。然而，新的发现表明RNA也具有类似的能力。我们试图了解RNA如何执行历史上仅归因于蛋白质的复杂功能。要做到这一点，需要在三维空间中观察RNA结构，这一壮举是通过诱导非常纯的RNA样品形成有序的晶体来完成的，这些晶体通过X射线衍射进行分析。在我们的实验室中，我们正在开发一种新的实验系统，以生长与蛋白质结合的RNA分子晶体，而不是通常的未结合状态。该系统有可能使我们能够快速确定许多新的RNA结构。我们期望这些结构将为我们提供对RNA在基本细胞过程中的功能作用的基本见解。 ***