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: 2006
• 资助国家: 加拿大
• 起止时间: 2006-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=337425
• 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)

所有生物体中最基本的活动之一是根据DNA中的指令制造蛋白质。蛋白质是一种分子机器，它执行生物体维持生命所需的许多功能。DNA转化为蛋白质是复杂的。特别是，DNA包含“非编码”信息区域（不包含指定蛋白质序列信息的区域），必须在蛋白质合成之前去除。如果不能去除非编码区，就会导致蛋白质受损，无法发挥作用，事实上，这往往与癌症等疾病有关。基于DNA信息制造蛋白质分两步进行：首先，DNA被复制成RNA（类似于DNA），其次，RNA被用作指定特定蛋白质的模板。非编码区在RNA阶段被移除，这一过程被称为前mrna剪接。本研究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剪接过程的一种手段。这项技术的基础是观察到两个荧光分子在靠近时可以交换能量，而在远离时则不能。通过在RNA的两端放置一个荧光分子，就有可能精确地测量RNA何时改变形状。利用这种荧光RNA，我们将解决pre-mRNA剪接中的基本问题，例如RNA改变结构的信号以及结构变化如何用于促进剪接。这项技术将为生物化学家提供一系列关于pre-mRNA剪接过程的令人兴奋的新信息，但它也将走得更远：RNA在许多其他过程中起着重要作用，这种荧光技术将适用于在任何情况下研究RNA。由于它的速度和灵敏度，荧光RNA将为RNA生物化学的整个领域开辟新的研究方向。（更多信息，请访问http://web.unbc.ca/~rader）