ArticleNature communications2018
Targeting RNA structure in SMN2 reverses spinal muscular atrophy molecular phenotypes.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
37 citing papers in PubMed.
- Unraveling the Multifunctional Therapeutic Potential of Topsentin: A Marine-derived Versatile Scaffold.Mini reviews in medicinal chemistry · 2026Review
- RNA-binding proteins as therapeutic targets in cancer.RNA biology · 2025Review
- Causes, functions, and therapeutic possibilities of RNA secondary structure ensembles and alternative states.Cell chemical biology · 2024Review
- RNA in situ conformation sequencing reveals novel long-range RNA structures with impact on splicing.RNA (New York, N.Y.) · 2023Article
- Diverse targets of SMN2-directed splicing-modulating small molecule therapeutics for spinal muscular atrophy.Nucleic acids research · 2023Article
- Conformational dynamics of RNA G4C2 and G2C4 repeat expansions causing ALS/FTD using NMR and molecular dynamics studies.Nucleic acids research · 2023Article
- Using CRISPR/Cas to enhance gene expression for crop trait improvement by editing miRNA targets.Journal of experimental botany · 2023Article
- Structure and function analysis of Sam68 and hnRNP A1 synergy in the exclusion of exon 7 from SMN2 transcripts.Protein science : a publication of the Protein Society · 2023Article
- Gene Therapy in ALS and SMA: Advances, Challenges and Perspectives.International journal of molecular sciences · 2023Review
- Long-range RNA structures in the human transcriptome beyond evolutionarily conserved regions.PeerJ · 2023Article
- RNA Transcript Diversity in Neuromuscular Research.Journal of neuromuscular diseases · 2023Review
- A toolkit for the identification of NEAT1_2/paraspeckle modulators.Nucleic acids research · 2022Article
- Multiassay Profiling of a Focused Small Molecule Library Reveals Predictive Bidirectional Modulation of the lncRNA MALAT1 Triplex StabilityACS chemical biology · 2022Article
- Secondary structures in RNA synthesis, splicing and translation.Computational and structural biotechnology journal · 2022Review
- Review
- Exploring the Druggability of Conserved RNA Regulatory Elements in the SARS-CoV-2 Genome.Angewandte Chemie (International ed. in English) · 2021Article
- High Concentration of an ISS-N1-Targeting Antisense Oligonucleotide Causes Massive Perturbation of the Transcriptome.International journal of molecular sciences · 2021Article
- RNA Engineering for Public Health: Innovations in RNA-Based Diagnostics and Therapeutics.Annual review of chemical and biomolecular engineering · 2021Article
- Conserved long-range base pairings are associated with pre-mRNA processing of human genes.Nature communications · 2021Article
- RNA-Targeting Splicing Modifiers: Drug Development and Screening Assays.Molecules (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
24 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Modification of SMN2 exon 7 (E7) splicing is a validated therapeutic strategy against spinal muscular atrophy (SMA). However, a target-based approach to identify small-molecule E7 splicing modifiers has not been attempted, which could reveal novel therapies with improved mechanistic insight. Here, we chose as a target the stem-loop RNA structure TSL2, which overlaps with the 5' splicing site of E7. A small-molecule TSL2-binding compound, homocarbonyltopsentin (PK4C9), was identified that increases E7 splicing to therapeutic levels and rescues downstream molecular alterations in SMA cells. High-resolution NMR combined with molecular modelling revealed that PK4C9 binds to pentaloop conformations of TSL2 and promotes a shift to triloop conformations that display enhanced E7 splicing. Collectively, our study validates TSL2 as a target for small-molecule drug discovery in SMA, identifies a novel mechanism of action for an E7 splicing modifier, and sets a precedent for other splicing-mediated diseases where RNA structure could be similarly targeted.
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