Aberrant pre-mRNA splicing as a cause of human disease

Alternative pre-messenger RNA (pre-mRNA) splicing is one of the most important mechanisms to generate multiple RNA isoforms from the surprisingly small number of human genes. A detailed analysis of transcript isoforms shows that alternative missplicing is the cause or consequence of an increasing number of human diseases. Dynamic complexes composed of pre-mRNA and regulatory proteins form on the pre-mRNA and dictate alternative splice site selection. The composition of these complexes depends on the concentration of regulatory factors, their phosphorylation state, and interaction with RNA. It is possible to influence alternative splicing in vivo by changing the concentration of regulatory factors, altering their phosphorylation state, or blocking mRNA sequences with oligonucleotides, which offers the possibility for treatment of diseases caused by missplicing.