The spliceosome: a novel multi-faceted target for therapy.
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.
Tazi
Jamal
J
Institut de Génétique Moléculaire de Montpellier (IGMM), UMR 5535, IFR 122, Centre National de Recherche Scientifique (CNRS), France. tazi@igmm.cnrs.fr
Durand
Sébastien
S
Jeanteur
Philippe
P
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015195:Drug Design; D006801:Humans; D007438:Introns / Q000235:genetics; D010766:Phosphorylation; D012326:RNA Splicing / Q000235:genetics; D017381:Spliceosomes / Q000187:drug effects* / Q000378:metabolism*
D000255:Adenosine Triphosphate