Alternative pre-mRNA splicing in the human system: unexpected role of repetitive sequences as regulatory elements

Alternative splicing is a process by which multiple messenger RNAs (mRNAs) are generated from a single pre-mRNA, resulting in functionally distinct protein products. This is accomplished by the differential recognition of splice sites in the pre-mRNA, often regulated in a tissue- or development-specific manner. Alternative splicing constitutes not only an important mechanism in controlling gene expression in humans, but also an essential source for increasing proteome diversity. In this review we summarize the underlying mechanistic principles, focussing on the cis-acting regulatory elements. In particular, the role of short sequence repeats, which are often polymorphic, in splicing regulation is discussed.