6HMI

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

6HMI の概要

• エントリーDOI: 10.2210/pdb6hmi/pdb
• NMR情報: BMRB: 34311
• 分子名称: RNA (5'-R(*AP*UP*AP*CP*(PSU)P*(PSU)P*AP*CP*CP*UP*G)-3'), RNA (5'-R(*GP*GP*AP*GP*UP*AP*AP*GP*UP*CP*U)-3') (2 entities in total)
• 機能のキーワード: weak 5'-splice site, u1 snrna, spinal muscular atrophy, bulge nucleotide, rna
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 6975.24

構造登録者

Campagne, S.,Allain, F.H. (登録日: 2018-09-12, 公開日: 2019-08-14, 最終更新日: 2024-06-19)

主引用文献

Campagne, S.,Boigner, S.,Rudisser, S.,Moursy, A.,Gillioz, L.,Knorlein, A.,Hall, J.,Ratni, H.,Clery, A.,Allain, F.H.
Structural basis of a small molecule targeting RNA for a specific splicing correction.
Nat.Chem.Biol., 15:1191-1198, 2019

PubMed Abstract: 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.

PubMed: 31636429
DOI: 10.1038/s41589-019-0384-5

実験手法

SOLUTION NMR