Alternativesplicinganditspotentialeffectsonproteinstructure.pptVIP

Alternative splicing and its potential effects on protein structure. Pedro R. Romero et al. PNAS 2006;103:8390-8395 ?2006 by National Academy of Sciences Alternative splicing and its potential effects on protein structure. During transcription, RNA is generated from the chromosome’s genetic material. This piece of RNA forms the basis for the mRNA that will be translated into proteins, hence the designation “pre-mRNA.” mRNA is composed of terminal UTRs, which help guide and regulate the translation process, and a central coding region, which is translated into the corresponding protein product. Eukaryotic genes contain fragments that are not used in the translation process, called introns, and regions that will become part of the final mRNA, called exons. Here exons are shown as colored cylinders. The mRNA to be translated is assembled from pre-mRNA by splicing the introns away, so that only the exons remain, as shown in both sides of the image. During alternative splicing, some exons also can be partially or completely spliced away, as can be seen in the path marked by purple arrows to the right of the figure, where the red exon and two of the UTR exons are “skipped,” generating a shorter mRNA and hence a shorter protein product. The different products of alternative splicing are called isoforms. In this work, the region missing in isoform 2 because of alternative splicing is called an AS region. The generation of isoforms by alternative splicing poses potential problems for the structural stability of globular proteins, because protein folding is a strongly cooperative process. Indeed, the absence of the red AS region in isoform 2 can potentially disturb the protein’s 3D structure very strongly, but few systematic studies of this effect have been carried out. Note: Although we have described this process in terms of removal of protein regions, the same argument can be made about insertion of AS regions, without loss of generality. ?