ArticleMolecular therapy. Nucleic acids2018
Antisense Oligonucleotide-Mediated Terminal Intron Retention of the SMN2 Transcript.
Article in Molecular therapy. Nucleic acids, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Oligonucleotides targeting the 3' splice site downstream of a microexon as an innovative therapy for autism.NAR molecular medicine · 2025Article
- Intron Retention: A Reemerging Paradigm in RNA Biology and Post-Transcriptional Gene Regulation.Genes · 2025Review
- 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
- Size matters: Fighting repeat expansion size in fragile X syndrome using antisense oligonucleotides.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- High Concentration or Combined Treatment of Antisense Oligonucleotides for Spinal Muscular Atrophy PerturbedGenes · 2022Article
- Antisense Oligonucleotide Induction of the hnRNPA1b Isoform Affects Pre-mRNA Splicing ofInternational journal of molecular sciences · 2022Article
- Polyglutamine Ataxias: Our Current Molecular Understanding and What the Future Holds for Antisense Therapies.Biomedicines · 2021Review
- Review
- TargetedBiomedicines · 2021Article
- 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
- Progress in the molecular pathogenesis and nucleic acid therapeutics for Parkinson's disease in the precision medicine era.Medicinal research reviews · 2020Review
- Removal of the Polyglutamine Repeat of Ataxin-3 by Redirecting pre-mRNA Processing.International journal of molecular sciences · 2019Article
- Systematic Approach to Developing Splice Modulating Antisense Oligonucleotides.International journal of molecular sciences · 2019Article
- In Vitro Validation of Phosphorodiamidate Morpholino Oligomers.Molecules (Basel, Switzerland) · 2019Article
- Profound analgesia is associated with a truncated peptide resulting from tissue specific alternative splicing of DRG CA8-204 regulated by an exon-level cis-eQTL.PLoS genetics · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The severe childhood disease spinal muscular atrophy (SMA) arises from the homozygous loss of the survival motor neuron 1 gene (SMN1). A homologous gene potentially encoding an identical protein, SMN2 can partially compensate for the loss of SMN1; however, the exclusion of a critical exon in the coding region during mRNA maturation results in insufficient levels of functional protein. The rate of transcription is known to influence the alternative splicing of gene transcripts, with a fast transcription rate correlating to an increase in alternative splicing. Conversely, a slower transcription rate is more likely to result in the inclusion of all exons in the transcript. Targeting SMN2 with antisense oligonucleotides to influence the processing of terminal exon 8 could be a way to slow transcription and induce the inclusion of exon 7. Interestingly, following oligomer treatment of SMA patient fibroblasts, we observed the inclusion of exon 7, as well as intron 7, in the transcript. Because the normal termination codon is located in exon 7, this exon/intron 7-SMN2 transcript should encode the normal protein and only carry a longer 3' UTR. Further studies showed the extra 3' UTR length contained a number of regulatory motifs that modify transcript and protein regulation, leading to translational repression of SMN. Although unlikely to provide therapeutic benefit for SMA patients, this novel technique for gene regulation could provide another avenue for the repression of undesirable gene expression in a variety of other diseases.
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