Differential Splicing, Disease and Drug Targets

O.      Villate; A.      Rastrojo; R.      Lopez-Diez; F.      Hernandez-Torres; B.      Aguado

Abstract

Genome complexity and diversity can be due to Alternative Splicing (AS), a process by which one gene can generate multiple mRNA isoforms and then several proteins. This is part of a normal process of variation on an individual, and when it is disrupted or modified, may trigger disease. To date, there are many pathologies described due to the effects of altered splicing isoforms, and effort is focused on the description of new ones. The design of drug target has to consider splicing, as in many occasions, a drug might have effect on different isoforms, instead of on the particular one implicated in the pathology. Interestingly, the strategies used to alter splicing can be used to modify a form towards the canonical one, or towards an aberrant one, when the latter one has a beneficial effect on the individual. Here we describe differential splicing, diseases produced by alterations on the mRNA isoforms, and drugs or methods used to restore these alterations.

Keywords: Alternative splicing, miRNA, siRNA, mRNA isoform, antisense oligonucleotide, SSOs