| Structural highlights
Function
[MGN_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). Remains associated with the mRNA after its export to the cytoplasm and require translation of the mRNA for removal. The heterodimer MAGOH-RBM8A interacts with PYM that function to enhance the translation of EJC-bearing spliced mRNAs by recruiting them to the ribosomal 48S preinitiation complex.[1] [2] [RBM8A_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). The heterodimer MAGOH-RBM8A interacts with PYM that function to enhance the translation of EJC-bearing spliced mRNAs by recruiting them to the ribosomal 48S preinitiation complex. Remains associated with mRNAs in the cytoplasm until the mRNAs engage the translation machinery. Its removal from cytoplasmic mRNAs requires translation initiation from EJC-bearing spliced mRNAs. Associates preferentially with mRNAs produced by splicing. Does not interact with pre-mRNAs, introns, or mRNAs produced from intronless cDNAs. Associates with both nuclear mRNAs and newly exported cytoplasmic mRNAs. Complex with MAGOH is a component of the nonsense mediated decay (NMD) pathway.[3] [4] [5] [6] [7]
Evolutionary Conservation
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Publication Abstract from PubMed
BACKGROUND: Splicing of pre-mRNA in eukaryotes imprints the resulting mRNA with a specific multiprotein complex, the exon-exon junction complex (EJC), at the sites of intron removal. The proteins of the EJC, Y14, Magoh, Aly/REF, RNPS1, Srm160, and Upf3, play critical roles in postsplicing processing, including nuclear export and cytoplasmic localization of the mRNA, and the nonsense-mediated mRNA decay (NMD) surveillance process. Y14 and Magoh are of particular interest because they remain associated with the mRNA in the same position after its export to the cytoplasm and require translation of the mRNA for removal. This tenacious, persistent, splicing-dependent, yet RNA sequence-independent, association suggests an important signaling function and must require distinct structural features for these proteins. RESULTS: We describe the high-resolution structure and biochemical properties of the highly conserved human Y14 and Magoh proteins. Magoh has an unusual structure comprised of an extremely flat, six-stranded anti-parallel beta sheet packed against two helices. Surprisingly, Magoh binds with high affinity to the RNP motif RNA binding domain (RBD) of Y14 and completely masks its RNA binding surface. CONCLUSIONS: The structure and properties of the Y14-Magoh complex suggest how the pre-mRNA splicing machinery might control the formation of a stable EJC-mRNA complex at splice junctions.
Structure of the Y14-Magoh core of the exon junction complex.,Lau CK, Diem MD, Dreyfuss G, Van Duyne GD Curr Biol. 2003 May 27;13(11):933-41. PMID:12781131[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Fribourg S, Gatfield D, Izaurralde E, Conti E. A novel mode of RBD-protein recognition in the Y14-Mago complex. Nat Struct Biol. 2003 Jun;10(6):433-9. PMID:12730685 doi:10.1038/nsb926
- ↑ 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
- ↑ Dostie J, Dreyfuss G. Translation is required to remove Y14 from mRNAs in the cytoplasm. Curr Biol. 2002 Jul 9;12(13):1060-7. PMID:12121612
- ↑ Gehring NH, Neu-Yilik G, Schell T, Hentze MW, Kulozik AE. Y14 and hUpf3b form an NMD-activating complex. Mol Cell. 2003 Apr;11(4):939-49. PMID:12718880
- ↑ Fribourg S, Gatfield D, Izaurralde E, Conti E. A novel mode of RBD-protein recognition in the Y14-Mago complex. Nat Struct Biol. 2003 Jun;10(6):433-9. PMID:12730685 doi:10.1038/nsb926
- ↑ 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
- ↑ 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
- ↑ Lau CK, Diem MD, Dreyfuss G, Van Duyne GD. Structure of the Y14-Magoh core of the exon junction complex. Curr Biol. 2003 May 27;13(11):933-41. PMID:12781131
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