2j0u

Structural highlights

Function

[IF4A3_HUMAN] ATP-dependent RNA helicase. Component of a splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of a few core proteins and several more peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Core components of the EJC, that remains bound to spliced mRNAs throughout all stages of mRNA metabolism, functions to mark the position of the exon-exon junction in the mature mRNA and thereby influences downstream processes of gene expression including mRNA splicing, nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). Constitutes at least part of the platform anchoring other EJC proteins to spliced mRNAs. Its RNA-dependent ATPase and RNA-helicase activities are induced by CASC3, but abolished in presence of the MAGOH/RBM8A heterodimer, thereby trapping the ATP-bound EJC core onto spliced mRNA in a stable conformation. The inhibition of ATPase activity by the MAGOH/RBM8A heterodimer increases the RNA-binding affinity of the EJC. Involved in translational enhancement of spliced mRNAs after formation of the 80S ribosome complex. Binds spliced mRNA in sequence-independent manner, 20-24 nucleotides upstream of mRNA exon-exon junctions. Shows higher affinity for single-stranded RNA in an ATP-bound core EJC complex than after the ATP is hydrolyzed.^{[1] [2] [3] [4] [5]} [CASC3_HUMAN] Component of a splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of a few core proteins and several more peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Core components of the EJC, that remains bound to spliced mRNAs throughout all stages of mRNA metabolism, functions to mark the position of the exon-exon junction in the mature mRNA and thereby influences downstream processes of gene expression including mRNA splicing, nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). Stimulates the ATPase and RNA-helicase activities of EIF4A3. Plays a role in the stress response by participating in cytoplasmic stress granules assembly and by favoring cell recovery following stress. Component of the dendritic ribonucleoprotein particles (RNPs) in hippocampal neurons (By similarity). May play a role in mRNA transport (By similarity). Binds spliced mRNA in sequence-independent manner, 20-24 nucleotides upstream of mRNA exon-exon junctions. Binds poly(G) and poly(U) RNA homopolymer.^{[6] [7]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

• Helicase

References

1. ↑ Shibuya T, Tange TO, Sonenberg N, Moore MJ. eIF4AIII binds spliced mRNA in the exon junction complex and is essential for nonsense-mediated decay. Nat Struct Mol Biol. 2004 Apr;11(4):346-51. Epub 2004 Mar 21. PMID:15034551 doi:http://dx.doi.org/10.1038/nsmb750
2. ↑ Gehring NH, Kunz JB, Neu-Yilik G, Breit S, Viegas MH, Hentze MW, Kulozik AE. Exon-junction complex components specify distinct routes of nonsense-mediated mRNA decay with differential cofactor requirements. Mol Cell. 2005 Oct 7;20(1):65-75. PMID:16209946 doi:http://dx.doi.org/S1097-2765(05)01554-6
3. ↑ Ballut L, Marchadier B, Baguet A, Tomasetto C, Seraphin B, Le Hir H. The exon junction core complex is locked onto RNA by inhibition of eIF4AIII ATPase activity. Nat Struct Mol Biol. 2005 Oct;12(10):861-9. Epub 2005 Sep 18. PMID:16170325 doi:http://dx.doi.org/nsmb990
4. ↑ Noble CG, Song H. MLN51 stimulates the RNA-helicase activity of eIF4AIII. PLoS One. 2007 Mar 21;2(3):e303. PMID:17375189 doi:http://dx.doi.org/10.1371/journal.pone.0000303
5. ↑ Lee HC, Choe J, Chi SG, Kim YK. Exon junction complex enhances translation of spliced mRNAs at multiple steps. Biochem Biophys Res Commun. 2009 Jul 3;384(3):334-40. doi:, 10.1016/j.bbrc.2009.04.123. Epub 2009 May 3. PMID:19409878 doi:http://dx.doi.org/10.1016/j.bbrc.2009.04.123
6. ↑ Baguet A, Degot S, Cougot N, Bertrand E, Chenard MP, Wendling C, Kessler P, Le Hir H, Rio MC, Tomasetto C. The exon-junction-complex-component metastatic lymph node 51 functions in stress-granule assembly. J Cell Sci. 2007 Aug 15;120(Pt 16):2774-84. Epub 2007 Jul 24. PMID:17652158 doi:http://dx.doi.org/10.1242/jcs.009225
7. ↑ Noble CG, Song H. MLN51 stimulates the RNA-helicase activity of eIF4AIII. PLoS One. 2007 Mar 21;2(3):e303. PMID:17375189 doi:http://dx.doi.org/10.1371/journal.pone.0000303
8. ↑ Bono F, Ebert J, Lorentzen E, Conti E. The crystal structure of the exon junction complex reveals how it maintains a stable grip on mRNA. Cell. 2006 Aug 25;126(4):713-25. PMID:16923391 doi:10.1016/j.cell.2006.08.006