ArticleAnnals of the New York Academy of Sciences2015
Splicing regulation in spinal muscular atrophy by an RNA structure formed by long-distance interactions.
Article in Annals of the New York Academy of Sciences, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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
40 citing papers in PubMed, 54 citations in OpenAlex.
- Nusinersen: the antisense oligonucleotide at the forefront of spinal muscular atrophy treatment.RNA biology · 2026Review
- Thermodynamic control of mismatch discrimination for extensive splicing regulation of PKM pre-mRNA.RNA (New York, N.Y.) · 2025Article
- Pre-mRNA Splicing Modulation by Antisense Oligonucleotides.Methods in molecular biology (Clifton, N.J.) · 2025Article
- e-RNA: a collection of web-servers for the prediction and visualisation of RNA secondary structure and their functional features.Nucleic acids research · 2023Article
- Thermodynamic characterization of naturally occurring RNA pentaloops.RNA (New York, N.Y.) · 2022Article
- Structural Context of a Critical Exon of Spinal Muscular Atrophy Gene.Frontiers in molecular biosciences · 2022Review
- Review
- High Concentration of an ISS-N1-Targeting Antisense Oligonucleotide Causes Massive Perturbation of the Transcriptome.International journal of molecular sciences · 2021Article
- [Scoliosis in spinal muscular atrophy].Der Orthopade · 2021Review
- Systematically Studying the Effect of Small Molecules Interacting with RNA in Cellular and Preclinical Models.ACS chemical biology · 2021Review
- Spinal muscular atrophy: Broad disease spectrum and sex-specific phenotypes.Biochimica et biophysica acta. Molecular basis of disease · 2021Review
- Structure of SRSF1 RRM1 bound to RNA reveals an unexpected bimodal mode of interaction and explains its involvement in SMN1 exon7 splicing.Nature communications · 2021Article
- A survey of transcripts generated by spinal muscular atrophy genes.Biochimica et biophysica acta. Gene regulatory mechanisms · 2020Review
- RNA in spinal muscular atrophy: therapeutic implications of targeting.Expert opinion on therapeutic targets · 2020Review
- Small molecule targeting of RNA structures in neurological disorders.Annals of the New York Academy of Sciences · 2020Review
- RNA-Targeted Therapies and High-Throughput Screening Methods.International journal of molecular sciences · 2020Review
- The First Orally Deliverable Small Molecule for the Treatment of Spinal Muscular Atrophy.Neuroscience insights · 2020Review
- Structural basis of a small molecule targeting RNA for a specific splicing correction.Nature chemical biology · 2019Article
- A novel role of U1 snRNP: Splice site selection from a distance.Biochimica et biophysica acta. Gene regulatory mechanisms · 2019Review
- Human Survival Motor Neuron genes generate a vast repertoire of circular RNAs.Nucleic acids research · 2019Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Humans carry two copies of the survival motor neuron gene: SMN1 and SMN2. Loss of SMN1 coupled with skipping of SMN2 exon 7 causes spinal muscular atrophy (SMA), a leading genetic disease associated with infant mortality. Our discovery of intronic splicing silencer N1 (ISS-N1) is a promising target, currently in a phase III clinical trial, for an antisense oligonucleotide-mediated splicing correction in SMA. We have recently shown that the first residue of ISS-N1 is locked in a unique RNA structure that we term ISTL1 (internal stem through long-distance interaction-1). Complementary strands of ISTL1 are separated from each other by 279 nucleotides. Using site-specific mutations and chemical structure probing, we confirmed the formation and functional significance of ISTL1. Located in the middle of intron 7, the 3' strand of ISTL1 falls within an inhibitory region that we term ISS-N2. We demonstrate that an antisense oligonucleotide-mediated sequestration of ISS-N2 fully corrects SMN2 exon 7 splicing and restores high levels of SMN in SMA patient cells. These results underscore the therapeutic potential of the regulatory information present in a secondary and high-order RNA structure of a human intron.
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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.