SR proteins as potential targets for therapy.

Serine- and arginine-rich (SR) proteins constitute a highly conserved family of pre-mRNA splicing factors that play key roles in the regulation of splice site selection, and thereby in the control of alternative splicing processes. In addition to conserved sequences at the splice junctions, splice site selection also depends upon different sets of auxiliary cis regulatory elements known as exonic and intronic splicing enhancers (ESEs and ISEs) or exonic and intronic silencers (ESSs and ISSs). Specific binding of SR proteins to their cognate splicing enhancers as well as binding of splicing repressor to silencer sequences serve to enhance or inhibit recognition of weak splice sites by the splicing machinery. Given that the vast majority of human genes contain introns and that most pre-mRNAs containing multiple exons undergo alternative splicing, mutations disrupting or creating such auxiliary elements can result in aberrant splicing events at the origin of various human diseases. In the past few years, numerous studies have reported several approaches allowing correction of such aberrant splicing events by targeting either the mutated sequences or the splicing regulators whose binding is affected by the mutation. The aim of the present review is to highlight the different means by which it is possible to modulate the activity of SR splicing factors and to bring out those holding the greatest promises for the development of therapeutic treatments.