Pre-mRNA splicing

Published on October 1, 2007 Reviewed on July 23, 2015   38 min

Other Talks in the Category: Biochemistry

The focus of this presentation is Nuclear Pre-mRNA Splicing. Splicing is an essential step in the expression of almost all genes and higher eukaryotes. We will begin by discussing the phenomenon of splicing and then discuss the mechanism by which it occurs. We will then shift to a discussion of how splicing, specifically alternative splicing, contributes to proteomic diversity. Finally, we will briefly discuss the role of splicing in messenger RNA surveillance and quality control.
This slide illustrates the structure of a typical higher eukaryotic protein coding gene. The transcribed region is shown in green and yellow, and the flanking regions are shown in red. The actual coding sequence, comprised of multiple exons, is shown in dark green. This sequence is interrupted by multiple intervening sequences, or introns, which are shown in yellow. Upon transcription, a pre-mRNA is produced which contains all of the exons and introns. To produce a functional messenger RNA, the introns must be removed by splicing, and the exons must be fused together in the order in which they were transcribed.
Here is a representation of a typical pre-mRNA intron. The intron contains three important sequence elements. Two of these elements, the five prime and three prime splice sites, define the boundaries of the intron. The third element, which resides just upstream of the three prime splice site, is called the branch point. As we will see in a moment, the branch point is essential for the chemistry of splicing. Comparison of the sequences of many thousands of introns has revealed that each of the three important intronic sites is characterized by a consensus sequence. However, with the exception of the first and last two nucleotides of the intron in the branch point itself, which are nearly invariant, considerable variation is allowed at all three sites. We will come back to this variability in splicing signals later.