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。蛋白质是执行有机体维持自身生存所需的许多功能的分子机器。然而，将DNA转换为蛋白质是复杂的。尤其是，DNA包含必须在蛋白质合成之前移除的非编码信息区域(不包含指定蛋白质序列的信息的区域)。如果不能去除非编码区域，就会导致蛋白质无法工作，实际上，通常与癌症等疾病有关。根据DNA信息制造蛋白质分两步进行：第一步，将DNA复制到RNA中(类似于DNA)，第二步，RNA是用来指定特定蛋白质的模板。在被称为Pre-RNA剪接的过程中，非编码区在RNA阶段被移除。这项提议的目的是开发一种新的技术来监测RNA结构的变化，作为研究Pre-RNA剪接过程的一种手段。这项技术是基于观察到两个荧光分子当它们靠近时可以交换能量，而当它们相隔很远时不能交换能量。通过在RNA的两端放置一个荧光分子，就可以准确地测量RNA何时改变形状。与这种荧光RNA一样，我们将解决前RNA剪接中的基本问题，如什么信号通知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mRNA剪接过程的令人兴奋的新信息，但它也将走得更远：RNARNA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。由于其速度和敏感性，荧光RNA有望为RNA生物化学的整个领域开辟新的研究思路。请访问http://web.unbc.ca/~rader)。

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)