4pcj
From Proteopedia
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| - | ''' | + | ==Modifications to toxic CUG RNAs induce structural stability and rescue mis-splicing in Myotonic Dystrophy== |
| + | <StructureSection load='4pcj' size='340' side='right' caption='[[4pcj]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4pcj]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PCJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PCJ FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4fnj|4fnj]]</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=4pcj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pcj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4pcj RCSB], [http://www.ebi.ac.uk/pdbsum/4pcj PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | CUG repeat expansions in the 3' UTR of dystrophia myotonica protein kinase (DMPK) cause myotonic dystrophy type 1 (DM1). As RNA, these repeats elicit toxicity by sequestering splicing proteins, such as MBNL1, into protein-RNA aggregates. Structural studies demonstrate that CUG repeats can form A-form helices, suggesting that repeat secondary structure could be important in pathogenicity. To evaluate this hypothesis, we utilized structure-stabilizing RNA modifications pseudouridine (Psi) and 2'-O-methylation to determine if stabilization of CUG helical conformations affected toxicity. CUG repeats modified with Psi or 2'-O-methyl groups exhibited enhanced structural stability and reduced affinity for MBNL1. Molecular dynamics and X-ray crystallography suggest a potential water-bridging mechanism for Psi-mediated CUG repeat stabilization. Psi modification of CUG repeats rescued mis-splicing in a DM1 cell model and prevented CUG repeat toxicity in zebrafish embryos. This study indicates that the structure of toxic RNAs has a significant role in controlling the onset of neuromuscular diseases. | ||
| - | + | Modifications to toxic CUG RNAs induce structural stability, rescue mis-splicing in a myotonic dystrophy cell model and reduce toxicity in a myotonic dystrophy zebrafish model.,deLorimier E, Coonrod LA, Copperman J, Taber A, Reister EE, Sharma K, Todd PK, Guenza MG, Berglund JA Nucleic Acids Res. 2014 Oct 10. pii: gku941. PMID:25303993<ref>PMID:25303993</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | == References == | |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Berglund, J A.]] | ||
| + | [[Category: Coonrod, L A.]] | ||
| + | [[Category: Reister, E E.]] | ||
| + | [[Category: Cug repeat]] | ||
| + | [[Category: Pseudou]] | ||
| + | [[Category: Tetraloop receptor]] | ||
Revision as of 11:20, 29 October 2014
Modifications to toxic CUG RNAs induce structural stability and rescue mis-splicing in Myotonic Dystrophy
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