ArticleNature chemical biology2015
SMN2 splice modulators enhance U1-pre-mRNA association and rescue SMA mice.
Article in Nature chemical biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 252 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
252 citing papers in PubMed, 1 synthesis or guideline pooled it, 426 citations in OpenAlex.
- RNA Drugs and RNA Targets for Small Molecules: Principles, Progress, and Challenges.Pharmacological reviews · 2020Pooled it
- Oral splicing modulator branaplam in Huntington's disease: a phase 2 randomized controlled trial.Nature medicine · 2026Trial
- An alternative splicing modulator decreases mutant HTT and improves the molecular fingerprint in Huntington's disease patient neurons.Nature communications · 2022Trial
- An orally available, brain penetrant, small molecule lowers huntingtin levels by enhancing pseudoexon inclusion.Nature communications · 2022Trial
- Age-dependent SMN expression in disease-relevant tissue and implications for SMA treatment.The Journal of clinical investigation · 2019Trial
- Review
- The U1 snRNP protein U1C and Helix H of U1 snRNA are critical for small molecule splicing modulator function.Nature communications · 2026Article
- Specificity and exon target space of splicing modifying compounds.Nature communications · 2026Article
- AI-Augmented Iterative Screening of Libraries Against RNA Targets (AISLAR) Boosts Discovery of SAR-Tractable RNA Binders and Rational Analog Design.Small science · 2026Article
- LSD1 inhibition ameliorates congenital dyserythropoietic anemia type II.Science translational medicine · 2026Article
- Targeting RNA binding proteins with small-molecule inhibitors: Advances, challenges, and therapeutic opportunities.Acta pharmaceutica Sinica. B · 2026Review
- The kinase inhibitor palbociclib binds to HIV TAR RNA with very low nanomolar affinity and exquisite specificity.Nucleic acids research · 2026Article
- RNA localization to nuclear speckles follows splicing logic.Nucleic acids research · 2026Article
- Small molecule splicing modulators that disrupt O-GlcNAc homeostasis.Nature communications · 2026Article
- MGTbind: a comprehensive database of molecular glue ternary interactome.Nucleic acids research · 2026Article
- Predicting small molecule-RNA interactions without RNA tertiary structures.Nature biotechnology · 2026Article
- Therapeutic strategies for spinal muscular atrophy: the history and future perspective.Frontiers in human neuroscience · 2026Review
- The Endo-GeneScreen platform identifies drug-like probes that regulate endogenous protein levels within physiological contexts.Nature communications · 2025Article
- RNA-binding proteins as therapeutic targets in cancer.RNA biology · 2025Review
- Systematic characterization of existing and novel inducible transgenic systems in human pluripotent stem cells after prolonged differentiation.bioRxiv : the preprint server for biology · 2025Article
192 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
- Erratum issued
Authors and funding
40 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Spinal muscular atrophy (SMA), which results from the loss of expression of the survival of motor neuron-1 (SMN1) gene, represents the most common genetic cause of pediatric mortality. A duplicate copy (SMN2) is inefficiently spliced, producing a truncated and unstable protein. We describe herein a potent, orally active, small-molecule enhancer of SMN2 splicing that elevates full-length SMN protein and extends survival in a severe SMA mouse model. We demonstrate that the molecular mechanism of action is via stabilization of the transient double-strand RNA structure formed by the SMN2 pre-mRNA and U1 small nuclear ribonucleic protein (snRNP) complex. The binding affinity of U1 snRNP to the 5' splice site is increased in a sequence-selective manner, discrete from constitutive recognition. This new mechanism demonstrates the feasibility of small molecule-mediated, sequence-selective splice modulation and the potential for leveraging this strategy in other splicing diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.