Human CWC22 escorts the helicase eIF4AIII to spliceosomes and promotes exon junction complex assembly

被引：88

作者：

Barbosa, Isabelle ^{[1
,2
]}

Haque, Nazmul ^{[3
]}

Fiorini, Francesca ^{[1
,2
]}

Barrandon, Charlotte ^{[1
,2
]}

Tomasetto, Catherine ^{[4
]}

Blanchette, Marco ^{[3
]}

Le Hir, Herve ^{[1
,2
]}

机构：

[1] Ecole Normale Super, CNRS, Inst Biol, UMR8197, Paris, France

[2] Ecole Normale Super, Inst Biol, INSERM, U1024, F-75231 Paris, France

[3] Stowers Inst Med Res, Kansas City, MO USA

[4] CNRS, Inst Genet & Biol Mol & Cellulaire, UMR7104, Illkirch Graffenstaden, France

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2012年 / 19卷 / 10期

关键词：

MESSENGER-RNA EXPORT; CORE COMPLEX; CONFORMATIONAL REARRANGEMENT; TRANSLATION INITIATION; MAMMALIAN-CELLS; ATPASE ACTIVITY; PROTEIN; TRANSCRIPTION; RECRUITMENT; DROSOPHILA;

D O I：

10.1038/nsmb.2380

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：983 / U29

页数：9

共 59 条

[1] Human eIF4AIII interacts with an eIF4G-like partner, NOM1, revealing an evolutionarily conserved function outside the exon junction complex [J].