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

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，它执行着生物体维持生命所需的许多功能。 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），这些区域必须在蛋白质合成之前去除。 如果不能去除非编码区，就会导致蛋白质损坏，无法工作，事实上，这些蛋白质经常与癌症等疾病有关。 基于DNA信息制造蛋白质分为两步：首先，DNA被复制成RNA（类似于DNA），其次，RNA被用作模板来指定特定的蛋白质。 在RNA阶段，非编码区在称为前mRNA剪接的过程中被去除。 该提案的目的是开发一种新的技术，用于监测RNA结构的变化，作为研究前体mRNA剪接过程的手段。 这项技术是基于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的每一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。 有了这种荧光RNA，我们将解决前体mRNA剪接中的基本问题，例如什么信号使RNA改变结构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前体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研究任何背景下的RNA。 由于它的速度和灵敏度，荧光RNA将打开整个RNA生物化学领域的新研究领域。 (For更多信息，请访问http：//web.unbc.ca/webrader）

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)