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| | ==Structure of SRSF1 RRM2 in complex with the RNA 5'-UGAAGGAC-3'== | | ==Structure of SRSF1 RRM2 in complex with the RNA 5'-UGAAGGAC-3'== |
| - | <StructureSection load='2m8d' size='340' side='right'caption='[[2m8d]], [[NMR_Ensembles_of_Models | 16 NMR models]]' scene=''> | + | <StructureSection load='2m8d' size='340' side='right'caption='[[2m8d]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2m8d]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M8D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M8D FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2m8d]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M8D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M8D FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SRSF1, ASF, SF2, SF2P33, SFRS1, OK/SW-cl.3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </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=2m8d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m8d OCA], [https://pdbe.org/2m8d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m8d RCSB], [https://www.ebi.ac.uk/pdbsum/2m8d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m8d ProSAT]</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=2m8d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m8d OCA], [https://pdbe.org/2m8d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m8d RCSB], [https://www.ebi.ac.uk/pdbsum/2m8d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m8d ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/SRSF1_HUMAN SRSF1_HUMAN]] Plays a role in preventing exon skipping, ensuring the accuracy of splicing and regulating alternative splicing. Interacts with other spliceosomal components, via the RS domains, to form a bridge between the 5'- and 3'-splice site binding components, U1 snRNP and U2AF. Can stimulate binding of U1 snRNP to a 5'-splice site-containing pre-mRNA. Binds to purine-rich RNA sequences, either the octamer, 5'-RGAAGAAC-3' (r=A or G) or the decamers, AGGACAGAGC/AGGACGAAGC. Binds preferentially to the 5'-CGAGGCG-3' motif in vitro. Three copies of the octamer constitute a powerful splicing enhancer in vitro, the ASF/SF2 splicing enhancer (ASE) which can specifically activate ASE-dependent splicing. Isoform ASF-2 and isoform ASF-3 act as splicing repressors.<ref>PMID:8223481</ref> <ref>PMID:8139654</ref>
| + | [https://www.uniprot.org/uniprot/SRSF1_HUMAN SRSF1_HUMAN] Plays a role in preventing exon skipping, ensuring the accuracy of splicing and regulating alternative splicing. Interacts with other spliceosomal components, via the RS domains, to form a bridge between the 5'- and 3'-splice site binding components, U1 snRNP and U2AF. Can stimulate binding of U1 snRNP to a 5'-splice site-containing pre-mRNA. Binds to purine-rich RNA sequences, either the octamer, 5'-RGAAGAAC-3' (r=A or G) or the decamers, AGGACAGAGC/AGGACGAAGC. Binds preferentially to the 5'-CGAGGCG-3' motif in vitro. Three copies of the octamer constitute a powerful splicing enhancer in vitro, the ASF/SF2 splicing enhancer (ASE) which can specifically activate ASE-dependent splicing. Isoform ASF-2 and isoform ASF-3 act as splicing repressors.<ref>PMID:8223481</ref> <ref>PMID:8139654</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Allain, F H.T]] | + | [[Category: Allain FHT]] |
| - | [[Category: Anczukow, O]] | + | [[Category: Anczukow O]] |
| - | [[Category: Clery, A]] | + | [[Category: Clery A]] |
| - | [[Category: Corrionero, A]] | + | [[Category: Corrionero A]] |
| - | [[Category: Daubner, G]] | + | [[Category: Daubner G]] |
| - | [[Category: Krainer, A R]] | + | [[Category: Krainer AR]] |
| - | [[Category: Moursy, A]] | + | [[Category: Moursy A]] |
| - | [[Category: Sinha, R]] | + | [[Category: Sinha R]] |
| - | [[Category: Valcarcel, J]] | + | [[Category: Valcarcel J]] |
| - | [[Category: Pseudo-rrm]]
| + | |
| - | [[Category: Rna binding protein-rna complex]]
| + | |
| - | [[Category: Rrm]]
| + | |
| - | [[Category: Sr protein]]
| + | |
| Structural highlights
Function
SRSF1_HUMAN Plays a role in preventing exon skipping, ensuring the accuracy of splicing and regulating alternative splicing. Interacts with other spliceosomal components, via the RS domains, to form a bridge between the 5'- and 3'-splice site binding components, U1 snRNP and U2AF. Can stimulate binding of U1 snRNP to a 5'-splice site-containing pre-mRNA. Binds to purine-rich RNA sequences, either the octamer, 5'-RGAAGAAC-3' (r=A or G) or the decamers, AGGACAGAGC/AGGACGAAGC. Binds preferentially to the 5'-CGAGGCG-3' motif in vitro. Three copies of the octamer constitute a powerful splicing enhancer in vitro, the ASF/SF2 splicing enhancer (ASE) which can specifically activate ASE-dependent splicing. Isoform ASF-2 and isoform ASF-3 act as splicing repressors.[1] [2]
Publication Abstract from PubMed
Serine/arginine (SR) proteins, one of the major families of alternative-splicing regulators in Eukarya, have two types of RNA-recognition motifs (RRMs): a canonical RRM and a pseudo-RRM. Although pseudo-RRMs are crucial for activity of SR proteins, their mode of action was unknown. By solving the structure of the human SRSF1 pseudo-RRM bound to RNA, we discovered a very unusual and sequence-specific RNA-binding mode that is centered on one alpha-helix and does not involve the beta-sheet surface, which typically mediates RNA binding by RRMs. Remarkably, this mode of binding is conserved in all pseudo-RRMs tested. Furthermore, the isolated pseudo-RRM is sufficient to regulate splicing of about half of the SRSF1 target genes tested, and the bound alpha-helix is a pivotal element for this function. Our results strongly suggest that SR proteins with a pseudo-RRM frequently regulate splicing by competing with, rather than recruiting, spliceosome components, using solely this unusual RRM.
Isolated pseudo-RNA-recognition motifs of SR proteins can regulate splicing using a noncanonical mode of RNA recognition.,Clery A, Sinha R, Anczukow O, Corrionero A, Moursy A, Daubner GM, Valcarcel J, Krainer AR, Allain FH Proc Natl Acad Sci U S A. 2013 Jul 23;110(30):E2802-11. doi:, 10.1073/pnas.1303445110. Epub 2013 Jul 8. PMID:23836656[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Zuo P, Manley JL. Functional domains of the human splicing factor ASF/SF2. EMBO J. 1993 Dec;12(12):4727-37. PMID:8223481
- ↑ Kohtz JD, Jamison SF, Will CL, Zuo P, Luhrmann R, Garcia-Blanco MA, Manley JL. Protein-protein interactions and 5'-splice-site recognition in mammalian mRNA precursors. Nature. 1994 Mar 10;368(6467):119-24. PMID:8139654 doi:http://dx.doi.org/10.1038/368119a0
- ↑ Clery A, Sinha R, Anczukow O, Corrionero A, Moursy A, Daubner GM, Valcarcel J, Krainer AR, Allain FH. Isolated pseudo-RNA-recognition motifs of SR proteins can regulate splicing using a noncanonical mode of RNA recognition. Proc Natl Acad Sci U S A. 2013 Jul 23;110(30):E2802-11. doi:, 10.1073/pnas.1303445110. Epub 2013 Jul 8. PMID:23836656 doi:http://dx.doi.org/10.1073/pnas.1303445110
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