The molecular mechanism of U6 snRNA activation for pre-mRNA splicing

U6 snRNA激活前mRNA剪接的分子机制

• 批准号: 298521-2006
• 负责人: Rader, Stephen
• 金额: $ 2.82万
• 依托单位: University of Northern British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2008
• 资助国家: 加拿大
• 起止时间: 2008-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=396170
• 关键词: molecular; mechanism; U6; snRNA; activation

One of the most basic activities in all organisms is to make proteins based on the instructions in DNA.  Proteins are the molecular machines that execute many of the functions that an organism needs to keep itself alive.  The conversion of DNA into proteins is complicated.  In particular, the DNA contains regions of "non-coding" information (areas that do not contain information specifying protein sequences) that must be removed prior to protein synthesis.  Failure to remove the non-coding regions leads to corrupted proteins that do not work and, in fact, are frequently associated with diseases such as cancer.  Making proteins based on DNA information takes place in two steps: first, DNA is copied into RNA (which is similar to DNA), and, second, RNA is used as a template to specify a particular protein.  Non-coding regions are removed during the RNA stage in a process known as pre-mRNA splicing.  The object of this proposal is to develop a new technology for monitoring changes in the structure of RNA as a means to investigate the process of pre-mRNA splicing.  This technology is based on the observation that two fluorescent molecules can exchange energy when they are close together but not when they are far apart.  By putting a fluorescent molecule at each end of the RNA, it will be possible to measure exactly when the RNA changes shape.  With this fluorescent RNA, we will address fundamental questions in pre-mRNA splicing, such as what signals the RNA to change structure and how the structural change is used in promoting splicing.  This technique will provide biochemists with an exciting array of new information about the process of pre-mRNA splicing, but it will also go farther:  RNA plays an important role in many other processes, and this fluorescent technique will be applicable to studying RNA in any context.  Because of its speed and sensitivity, fluorescent RNA stands to open up entire fields of RNA biochemistry to new lines of investigation.  (For more information, visit http://web.unbc.ca/~rader)

所有生物体最基本的活动之一是根据 DNA 的指令制造蛋白质。  蛋白质是执行生物体维持自身生存所需的许多功能的分子机器。  DNA 转化为蛋白质的过程非常复杂。  特别是，DNA 包含“非编码”信息区域（不包含指定蛋白质序列的信息的区域），必须在蛋白质合成之前将其去除。  未能去除非编码区域会导致蛋白质被破坏而无法发挥作用，事实上，这些蛋白质经常与癌症等疾病相关。  根据 DNA 信息制造蛋白质分为两个步骤：首先，DNA 被复制成 RNA（与 DNA 类似），其次，RNA 被用作模板来指定特定的蛋白质。  非编码区在 RNA 阶段被去除，这一过程被称为前 mRNA 剪接。  该提案的目的是开发一种监测 RNA 结构变化的新技术，作为研究前 mRNA 剪接过程的手段。  该技术基于这样的观察：两个荧光分子在靠近时可以交换能量，但在远离时则不能交换能量。  通过在 RNA 的每一端放置一个荧光分子，就可以准确测量 RNA 何时改变形状。  借助这种荧光 RNA，我们将解决 mRNA 前体剪接中的基本问题，例如什么信号发出 RNA 改变结构以及如何利用结构变化来促进剪接。  这项技术将为生物化学家提供一系列关于前 mRNA 剪接过程的令人兴奋的新信息，但它还会走得更远：RNA 在许多其他过程中发挥着重要作用，这种荧光技术将适用于研究任何情况下的 RNA。  由于其速度和灵敏度，荧光 RNA 必将为 RNA 生物化学的整个领域开辟新的研究领域。  （欲了解更多信息，请访问http://web.unbc.ca/~rader）