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2m8d

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Structure of SRSF1 RRM2 in complex with the RNA 5'-UGAAGGAC-3'

Structural highlights

2m8d is a 2 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2m8d"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <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='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>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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>
 == Function ==

2m8d

From Proteopedia

Current revision

Structure of SRSF1 RRM2 in complex with the RNA 5'-UGAAGGAC-3'

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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