ArticleRNA biology
Alternative splicing in spinal muscular atrophy underscores the role of an intron definition model.
Article in RNA biology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Economic evidence on the cost-effectiveness of newborn screening for spinal muscular atrophy: a systematic review.European journal of pediatrics · 2025Pooled it
- Nusinersen: the antisense oligonucleotide at the forefront of spinal muscular atrophy treatment.RNA biology · 2026Review
- Pre-mRNA Splicing Modulation by Antisense Oligonucleotides.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Spinal muscular atrophy: Broad disease spectrum and sex-specific phenotypes.Biochimica et biophysica acta. Molecular basis of disease · 2021Review
- RNA in spinal muscular atrophy: therapeutic implications of targeting.Expert opinion on therapeutic targets · 2020Review
- A survey of transcripts generated by spinal muscular atrophy genes.Biochimica et biophysica acta. Gene regulatory mechanisms · 2020Review
- The First Orally Deliverable Small Molecule for the Treatment of Spinal Muscular Atrophy.Neuroscience insights · 2020Review
- AIDE: annotation-assisted isoform discovery with high precision.Genome research · 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
- Ultra-deep sequencing reveals pre-mRNA splicing as a sequence driven high-fidelity process.PloS one · 2019Article
- High-affinity RNA targets of the Survival Motor Neuron protein reveal diverse preferences for sequence and structural motifs.Nucleic acids research · 2018Article
- Targeting RNA structure in SMN2 reverses spinal muscular atrophy molecular phenotypes.Nature communications · 2018Article
- Pre-mRNA Splicing Modulation by Antisense Oligonucleotides.Methods in molecular biology (Clifton, N.J.) · 2018Article
- Mechanism of Splicing Regulation of Spinal Muscular Atrophy Genes.Advances in neurobiology · 2018Review
- Activation of a cryptic 5' splice site reverses the impact of pathogenic splice site mutations in the spinal muscular atrophy gene.Nucleic acids research · 2017Article
- Binding to SMN2 pre-mRNA-protein complex elicits specificity for small molecule splicing modifiers.Nature communications · 2017Article
- How the discovery of ISS-N1 led to the first medical therapy for spinal muscular atrophy.Gene therapy · 2017Review
- Faulty RNA splicing: consequences and therapeutic opportunities in brain and muscle disorders.Human genetics · 2017Review
- Diverse role of survival motor neuron protein.Biochimica et biophysica acta. Gene regulatory mechanisms · 2017Review
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Authors and funding
2 authors at 1 institution in 1 country.
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Abstract
Humans have two nearly identical copies of the Survival Motor Neuron (SMN) gene: SMN1 and SMN2. The two SMN genes code for identical proteins; however, SMN2 predominantly generates a shorter transcript due to skipping of exon 7, the last coding exon. Skipping of SMN2 exon 7 leads to production of a truncated SMN protein that is highly unstable. The inability of SMN2 to compensate for the loss of SMN1 results in spinal muscular atrophy (SMA), the second most prevalent genetic cause of infant mortality. Since SMN2 is almost universally present in SMA patients, correction of SMN2 exon 7 splicing holds the promise for cure. Consistently, SMN2 exon 7 splicing has emerged as one of the best studied splicing systems in humans. The vast amount of recent literature provides a clue that SMN2 exon 7 splicing is regulated by an intron definition mechanism, which does not require cross-exon communication as prerequisite for exon inclusion. Our conclusion is based on the prominent role of intronic cis-elements, some of them have emerged as the frontrunners among potential therapeutic targets of SMA. Further, the widely expressed T-cell-restricted intracellular antigen-1 (TIA1), a member of the Q-rich domain containing RNA-binding proteins, has recently been found to regulate SMN exon 7 splicing by binding to intron 7 sequences away from the 5′ ss. These findings make a strong argument for an "intron definition model", according to which regulatory sequences within a downstream intron are capable of enforcing exon inclusion even in the absence of a defined upstream 3′ ss of an alternatively spliced exon.
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