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==Solution structure of the RNA duplex formed by the 5'-end of U1snRNA and the 5'-splice site of SMN2 exon7 in complex with the SMN-C5 splicing modifier==
<StructureSection load='6hmo' size='340' side='right'caption='[[6hmo]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6hmo]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HMO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HMO FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GDZ:2-(8-fluoranyl-2-methyl-imidazo[1,2-a]pyridin-6-yl)-7-(4-methylpiperazin-1-yl)pyrido[1,2-a]pyrimidin-4-one'>GDZ</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PSU:PSEUDOURIDINE-5-MONOPHOSPHATE'>PSU</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6hmo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hmo OCA], [http://pdbe.org/6hmo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hmo RCSB], [http://www.ebi.ac.uk/pdbsum/6hmo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hmo ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Splicing modifiers promoting SMN2 exon 7 inclusion have the potential to treat spinal muscular atrophy, the leading genetic cause of infantile death. These small molecules are SMN2 exon 7 selective and act during the early stages of spliceosome assembly. Here, we show at atomic resolution how the drug selectively promotes the recognition of the weak 5' splice site of SMN2 exon 7 by U1 snRNP. The solution structure of the RNA duplex formed following 5' splice site recognition in the presence of the splicing modifier revealed that the drug specifically stabilizes a bulged adenine at this exon-intron junction and converts the weak 5' splice site of SMN2 exon 7 into a stronger one. The small molecule acts as a specific splicing enhancer cooperatively with the splicing regulatory network. Our investigations uncovered a novel concept for gene-specific alternative splicing correction that we coined 5' splice site bulge repair.

Structural basis of a small molecule targeting RNA for a specific splicing correction.,Campagne S, Boigner S, Rudisser S, Moursy A, Gillioz L, Knorlein A, Hall J, Ratni H, Clery A, Allain FH Nat Chem Biol. 2019 Dec;15(12):1191-1198. doi: 10.1038/s41589-019-0384-5. Epub, 2019 Oct 21. PMID:31636429<ref>PMID:31636429</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6hmo" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Allain, F H]]
[[Category: Campagne, S]]
[[Category: 5'-splice site bulge repair]]
[[Category: Bulge nucleotide]]
[[Category: Rna]]
[[Category: Spinal muscular atrophy]]
[[Category: Splicing modifier]]
[[Category: U1 snrna]]