The spliceosome: a novel multi-faceted target for therapy

J. Tazi (1) , S. Durand , P. Jeanteur (1)

1 IGMM - Institut de Génétique Moléculaire de Montpellier

The spliceosome is a dynamic and flexible ribonucleoprotein enzyme that removes intronic sequences in a regulated manner. Spliceosome action enables one stretch of genomic DNA sequence to yield several mRNAs that encode different proteins. It depends on a flexible mechanism for selecting splice sites, which calls for regulatory sequences (splicing enhancers or silencers) recognized by cognate trans-acting protein factors and constitutive ribonucleoprotein devices to build up the catalytic core. The identification of both types of elements now offers a comprehensive insight into how the spliceosome is adapted to carry out the removal of different introns and suggests novel therapeutic targets to, ultimately, restore a physiological pattern of alternatively spliced variants in a large repertoire of pathologies.

Mots clés: Adenosine Triphosphate/metabolism Animals *Drug Design Humans Introns/genetics Phosphorylation RNA Splicing/genetics Spliceosomes/*drug effects/*metabolism

Domaines: Biochimie, Biologie Moléculaire

J. Tazi, S. Durand, P. Jeanteur. The spliceosome: a novel multi-faceted target for therapy. Trends in Biochemical Sciences, 2005, 30 (8), pp.469--78. ⟨10.1016/j.tibs.2005.06.002⟩. ⟨hal-02262238⟩