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

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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)