Alternative splicing - principles, functional consequences and therapeutic implications

Protein-coding genes in higher eukaryotes are transcribed as pre-mRNA in which the coding regions (exons) are separated by non-coding segments (introns). The exons are connected to form the mature mRNA in a process called splicing. In the case of alternative splicing an exon can be either included or skipped from the mature transcript leading to formation of several mRNAs from a single pre-mRNA. As over 90 % of all human genes are alternatively spliced, alternative splicing dramatically increases proteome diversity and fulfills important regulatory functions. This is underlined by mutations that interfere with splicing regulation and directly correlate with the formation of several diseases. Correction of these disturbed splicing processes has emerged as a promising therapeutic concept and has led to the development of several drugs that are currently being tested in clinical trials. © Georg Thieme Verlag KG Stuttgart New York ISSN 0012-0472.