ArticleNucleic acids research2013
An intronic structure enabled by a long-distance interaction serves as a novel target for splicing correction in spinal muscular atrophy.
Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
59 citing papers in PubMed, 85 citations in OpenAlex.
- Nusinersen: the antisense oligonucleotide at the forefront of spinal muscular atrophy treatment.RNA biology · 2026Review
- RNAStructuromeDB: a transcriptome-wide database of predicted RNA secondary structures with integrated APIs for functional annotation and RNA-targeted drug discovery.NAR genomics and bioinformatics · 2026Article
- Navigating the next frontier in biomedicine: breakthroughs and insights in nucleic acid therapeutics.Chemical science · 2026Review
- A therapeutic antisense oligonucleotide encompassing 2'-NAR molecular medicine · 2026Article
- Pre-mRNA Splicing Modulation by Antisense Oligonucleotides.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Non-Coding RNA in Tumor Cells and Tumor-Associated Myeloid Cells-Function and Therapeutic Potential.International journal of molecular sciences · 2024Review
- A super minigene with a short promoter and truncated introns recapitulates essential features of transcription and splicing regulation of the SMN1 and SMN2 genes.Nucleic acids research · 2024Article
- Causes, functions, and therapeutic possibilities of RNA secondary structure ensembles and alternative states.Cell chemical biology · 2024Review
- U1 snRNA interactions with deep intronic sequences regulate splicing of multiple exons of spinal muscular atrophy genes.Frontiers in neuroscience · 2024Article
- Development of 2'-O-Methyl and LNA Antisense Oligonucleotides forBiomedicines · 2023Article
- PRMT inhibitor promotes SMN2 exon 7 inclusion and synergizes with nusinersen to rescue SMA mice.EMBO molecular medicine · 2023Article
- SMN regulates GEMIN5 expression and acts as a modifier of GEMIN5-mediated neurodegeneration.Acta neuropathologica · 2023Article
- Diverse targets of SMN2-directed splicing-modulating small molecule therapeutics for spinal muscular atrophy.Nucleic acids research · 2023Article
- How does precursor RNA structure influence RNA processing and gene expression?Bioscience reports · 2023Review
- Antisense oligonucleotides: a novel Frontier in pharmacological strategy.Frontiers in pharmacology · 2023Review
- Systematic characterization of short intronic splicing-regulatory elements in SMN2 pre-mRNA.Nucleic acids research · 2022Article
- History of development of the life-saving drug "Nusinersen" in spinal muscular atrophy.Frontiers in cellular neuroscience · 2022Review
- 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
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Here, we report a long-distance interaction (LDI) as a critical regulator of alternative splicing of Survival Motor Neuron 2 (SMN2) exon 7, skipping of which is linked to spinal muscular atrophy (SMA), a leading genetic disease of children and infants. We show that this LDI is linked to a unique intra-intronic structure that we term internal stem through LDI-1 (ISTL1). We used site-specific mutations and Selective 2'-Hydroxyl Acylation analyzed by Primer Extension to confirm the formation and functional significance of ISTL1. We demonstrate that the inhibitory effect of ISTL1 is independent of hnRNP A1/A2B1 and PTB1 previously implicated in SMN2 exon 7 splicing. We show that an antisense oligonucleotide-mediated sequestration of the 3' strand of ISTL1 fully corrects SMN2 exon 7 splicing and restores high levels of SMN and Gemin2, a SMN-interacting protein, in SMA patient cells. Our results also reveal that the 3' strand of ISTL1 and upstream sequences constitute an inhibitory region that we term intronic splicing silencer N2 (ISS-N2). This is the first report to demonstrate a critical role of a structure-associated LDI in splicing regulation of an essential gene linked to a genetic disease. Our findings expand the repertoire of potential targets for an antisense oligonucleotide-mediated therapy of SMA.
Indexed as
Identifiers
What OpenQuestion holds
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.