6hmi | pdb_00006hmi

Solution structure of the RNA duplex formed by the 5'-end of U1snRNA and the 5'-splice site of SMN2 exon7

spinqualitylabelsall models 6hmi Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6hmi 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 Ligands: PSU Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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