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| | <StructureSection load='6yvh' size='340' side='right'caption='[[6yvh]], [[Resolution|resolution]] 3.19Å' scene=''> | | <StructureSection load='6yvh' size='340' side='right'caption='[[6yvh]], [[Resolution|resolution]] 3.19Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6yvh]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YVH OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6YVH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6yvh]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YVH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YVH FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CWC22, KIAA1604, NCM ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CWC27, SDCCAG10, UNQ438/PRO871 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), EIF4A3, DDX48, KIAA0111 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.19Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA_helicase RNA helicase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.4.13 3.6.4.13] </span></td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6yvh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yvh OCA], [https://pdbe.org/6yvh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yvh RCSB], [https://www.ebi.ac.uk/pdbsum/6yvh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yvh ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6yvh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yvh OCA], [http://pdbe.org/6yvh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6yvh RCSB], [http://www.ebi.ac.uk/pdbsum/6yvh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6yvh ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CWC22_HUMAN CWC22_HUMAN]] Required for pre-mRNA splicing and for exon-junction complex (EJC) assembly. Hinders EIF4A3 from non-specifically binding RNA and escorts it to the splicing machinery to promote EJC assembly on mature mRNAs. Through its role in EJC assembly, required for nonsense-mediated mRNA decay.<ref>PMID:22959432</ref> <ref>PMID:22961380</ref> <ref>PMID:23236153</ref> [[http://www.uniprot.org/uniprot/IF4A3_HUMAN 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.<ref>PMID:15034551</ref> <ref>PMID:16209946</ref> <ref>PMID:16170325</ref> <ref>PMID:17375189</ref> <ref>PMID:19409878</ref> [[http://www.uniprot.org/uniprot/CWC27_HUMAN CWC27_HUMAN]] PPIases accelerate the folding of proteins. | + | [https://www.uniprot.org/uniprot/CWC22_HUMAN CWC22_HUMAN] Required for pre-mRNA splicing and for exon-junction complex (EJC) assembly. Hinders EIF4A3 from non-specifically binding RNA and escorts it to the splicing machinery to promote EJC assembly on mature mRNAs. Through its role in EJC assembly, required for nonsense-mediated mRNA decay.<ref>PMID:22959432</ref> <ref>PMID:22961380</ref> <ref>PMID:23236153</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6yvh" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6yvh" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Eukaryotic initiation factor 3D structures|Eukaryotic initiation factor 3D structures]] |
| | + | *[[Pre-mRNA splicing factors 3D structures|Pre-mRNA splicing factors 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: RNA helicase]]
| + | [[Category: Basquin J]] |
| - | [[Category: Basquin, J]] | + | [[Category: Busetto V]] |
| - | [[Category: Busetto, V]] | + | [[Category: Conti E]] |
| - | [[Category: Conti, E]] | + | [[Category: LeHir H]] |
| - | [[Category: LeHir, H]] | + | |
| - | [[Category: Ejc helicase]]
| + | |
| - | [[Category: Rna binding protein]]
| + | |
| Structural highlights
Function
CWC22_HUMAN Required for pre-mRNA splicing and for exon-junction complex (EJC) assembly. Hinders EIF4A3 from non-specifically binding RNA and escorts it to the splicing machinery to promote EJC assembly on mature mRNAs. Through its role in EJC assembly, required for nonsense-mediated mRNA decay.[1] [2] [3]
Publication Abstract from PubMed
Human CWC27 is an uncharacterized splicing factor and mutations in its gene are linked to retinal degeneration and other developmental defects. We identify the splicing factor CWC22 as the major CWC27 partner. Both CWC27 and CWC22 are present in published Bact spliceosome structures, but no interacting domains are visible. Here, the structure of a CWC27/CWC22 heterodimer bound to the exon junction complex (EJC) core component eIF4A3 is solved at 3A-resolution. According to spliceosomal structures, the EJC is recruited in the C complex, once CWC27 has left. Our 3D structure of the eIF4A3/CWC22/CWC27 complex is compatible with the Bact spliceosome structure but not with that of the C complex, where a CWC27 loop would clash with the EJC core subunit Y14. A CWC27/CWC22 building block might thus form an intermediate landing platform for eIF4A3 onto the Bact complex prior to its conversion into C complex. Knock-down of either CWC27 or CWC22 in immortalized retinal pigment epithelial cells affects numerous common genes, indicating that these proteins cooperate, targeting the same pathways. As the most up-regulated genes encode factors involved in inflammation, our findings suggest a possible link to the retinal degeneration associated with CWC27 deficiencies.
Structural and functional insights into CWC27/CWC22 heterodimer linking the exon junction complex to spliceosomes.,Busetto V, Barbosa I, Basquin J, Marquenet E, Hocq R, Hennion M, Paternina JA, Namane A, Conti E, Bensaude O, Le Hir H Nucleic Acids Res. 2020 Apr 24. pii: 5824608. doi: 10.1093/nar/gkaa267. PMID:32329775[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Steckelberg AL, Boehm V, Gromadzka AM, Gehring NH. CWC22 connects pre-mRNA splicing and exon junction complex assembly. Cell Rep. 2012 Sep 27;2(3):454-61. doi: 10.1016/j.celrep.2012.08.017. Epub 2012, Sep 6. PMID:22959432 doi:http://dx.doi.org/10.1016/j.celrep.2012.08.017
- ↑ Barbosa I, Haque N, Fiorini F, Barrandon C, Tomasetto C, Blanchette M, Le Hir H. Human CWC22 escorts the helicase eIF4AIII to spliceosomes and promotes exon junction complex assembly. Nat Struct Mol Biol. 2012 Oct;19(10):983-90. doi: 10.1038/nsmb.2380. Epub 2012, Sep 9. PMID:22961380 doi:http://dx.doi.org/10.1038/nsmb.2380
- ↑ Alexandrov A, Colognori D, Shu MD, Steitz JA. Human spliceosomal protein CWC22 plays a role in coupling splicing to exon junction complex deposition and nonsense-mediated decay. Proc Natl Acad Sci U S A. 2012 Dec 26;109(52):21313-8. doi:, 10.1073/pnas.1219725110. Epub 2012 Dec 10. PMID:23236153 doi:http://dx.doi.org/10.1073/pnas.1219725110
- ↑ Busetto V, Barbosa I, Basquin J, Marquenet E, Hocq R, Hennion M, Paternina JA, Namane A, Conti E, Bensaude O, Le Hir H. Structural and functional insights into CWC27/CWC22 heterodimer linking the exon junction complex to spliceosomes. Nucleic Acids Res. 2020 Apr 24. pii: 5824608. doi: 10.1093/nar/gkaa267. PMID:32329775 doi:http://dx.doi.org/10.1093/nar/gkaa267
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