Fiche publication
Date publication
octobre 2012
Auteurs
Membres identifiés du Cancéropôle Est :
Dr TOMASETTO Catherine
Tous les auteurs :
Barbosa I, Haque N, Fiorini F, Barrandon C, Tomasetto C, Blanchette M, Le Hir H
Lien Pubmed
Résumé
The exon-junction complex (EJC) functionally links splicing to subsequent mRNA localization, translation and stability. Sequence-independent binding of the EJC core to RNA is ensured by the DEAD-box helicase eIF4AIII. Here, we identified the splicing factor CWC22 as a new eIF4AIII partner in flies and humans. CWC22 coexists with eIF4AIII in large protein complexes distinct from EJCs. Recombinant CWC22 directly contacts eIF4AIII and prevents it from binding RNA. In vitro splicing assays revealed that CWC22 introduces eIF4AIII to spliceosomes before remodeling to facilitate eIF4AIII incorporation into the EJC. Finally, using knockdowns in vivo, we showed that CWC22 is essential for EJC assembly. We elucidated the initial step of EJC assembly and the duality of CWC22 function that hinders eIF4AIII from nonspecifically binding RNA and escorts it to the splicing machinery to promote EJC assembly on mature mRNAs.
Référence
Nat Struct Mol Biol. 2012 Oct;19(10):983-90
