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Schematic animation
of mutually exclusive exons»

Alternative Splicing

More than 5% of all genes can produce variant proteins by alternative splicing. The protein variants made by alternative splicing can have important functional differences. The protein variants may differ in the presence or absence of structural or functional domains. In some cases one splicing pathway can lead to a translatable mRNA, while the alternative splicing pathway results in a non-translatable mRNA.

Biologically important processes involve alternative splicing. The determination of sexes in Drosophila is for example partly determined at the level of alternative splicing. Many cell types in the human body express different versions of proteins because of alternative spicing. For example, the three different types of muscle cells in the human body make three different versions of the protein tropomyosin by alternative splicing.

Many principle variants of alternative splicing have been described. (see illustration) A pre-mRNA can for example contain two alternative 5' (or 3') exon-intron borders, which can be used to excise a shorter or longer version of an intron. Pre-mRNAs which contain more than two introns can also be spliced to include all exons in the mRNA, or to exclude one or several of the exons. The regulation of alternative splicing is not yet well known. In some cases, a specific protein is present that binds to one 3' splice site of an intron and hides it from the splicing factors. This leads to the usage of the alternative 3' splice site instead. In other cases, one of two alternative 5' splice sites is weaker than the other and much less often used. The usage of the weak splice site can be stimulated by the binding of SR proteins to an RNA sequence located close to the 5' splice site, thereby helping the splicing factors to find the weak 5' splice site.


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