The Crystal Structure of the Exon Junction Complex Reveals How It Maintains a Stable Grip on mRNA

European Molecular Biology Laboratory, EMBL, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
Cell (Impact Factor: 32.24). 09/2006; 126(4):713-25. DOI: 10.1016/j.cell.2006.08.006
Source: PubMed


The exon junction complex (EJC) plays a major role in posttranscriptional regulation of mRNA in metazoa. The EJC is deposited onto mRNA during splicing and is transported to the cytoplasm where it influences translation, surveillance, and localization of the spliced mRNA. The complex is formed by the association of four proteins (eIF4AIII, Barentsz [Btz], Mago, and Y14), mRNA, and ATP. The 2.2 A resolution structure of the EJC reveals how it stably locks onto mRNA. The DEAD-box protein eIF4AIII encloses an ATP molecule and provides the binding sites for six ribonucleotides. Btz wraps around eIF4AIII and stacks against the 5' nucleotide. An intertwined network of interactions anchors Mago-Y14 and Btz at the interface between the two domains of eIF4AIII, effectively stabilizing the ATP bound state. Comparison with the structure of the eIF4AIII-Btz subcomplex that we have also determined reveals that large conformational changes are required upon EJC assembly and disassembly.

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    • "In this context, it is tempting to draw a parallel between Vasa's role and the function of the helicase domain of the related DEAD box helicase eIF4AIII in nucleating the formation of the exon junction complex (EJC) on spliced mRNAs (Le Hir et al., 2000). In its ATP-bound closed conformation, the eIF4AIII core domain clamps on spliced mRNAs to provide a binding surface for other EJC components Mago, Y14, and Barentsz (Andersen et al., 2006; Bono et al., 2006). A similar situation can be envisaged during Amplifier assembly. "
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    • "Crystallographic analyses have revealed that related DEADbox proteins, such as Vasa (Sengoku et al., 2006), eIF4AIII (Bono et al., 2006), Mss116p (Del Campo and Lambowitz, 2009), DbpA (Henn et al., 2010), CYT-19 (Grohman et al., 2007), and YxiN (Theissen et al., 2008), adopt a compact conformation in the presence of RNA and the ATP analog AMPPNP. ATP binding and phosphate release are thought to control opening and closing of the helicase core (Andreou and Klostermeier, 2012). "
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    • "The EJC Is Part of Btz-, but Not Stau2-RNPs From the LC-MS data, we noted that eIF4AIII and Magoh were positive interactors for Btz; however, neither were found with Stau2 (Table S1). For Btz, this was expected as it is a core component of the EJC (Andersen et al., 2006; Bono et al., 2006; Le Hir and Sé raphin, 2008) and has been previously linked to mRNA localization (Macchi et al., 2003; van Eeden et al., 2001). The fourth EJC core component, Y14, was detected in Btz-RNPs but was below the threshold to make the cutoff. "
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