ArticleAmerican journal of human genetics2015
Improvement of SMN2 pre-mRNA processing mediated by exon-specific U1 small nuclear RNA.
Article in American journal of human genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 58 citations in OpenAlex.
- AAV2-mediated intravitreal delivery of exon-specific U1 snRNA rescues optic neuropathy in familial dysautonomia.Molecular therapy. Nucleic acids · 2026Article
- Using RNA-targeting CRISPR-Cas13 and engineered U1 systems to targetMolecular therapy. Nucleic acids · 2026Article
- RNA dysfunction in age-related macular degeneration: the role of U1 snRNP complex and neurodegenerative diseases.International journal of retina and vitreous · 2025Review
- Rescue of a panel of Hemophilia A-causing 5'ss splicing mutations by unique Exon-specific U1snRNA variants.Molecular medicine (Cambridge, Mass.) · 2025Article
- Rescue of common and rare exon 2 skipping variants of the GAA gene using modified U1 snRNA.Molecular medicine (Cambridge, Mass.) · 2025Article
- Strategies for programmable manipulation of alternative splicing.Current opinion in genetics & development · 2024Review
- Therapeutic targeting of RNA for neurological and neuromuscular disease.Genes & development · 2024Review
- Development of Engineered-U1 snRNA Therapies: Current Status.International journal of molecular sciences · 2023Review
- Programmable macromolecule-based RNA-targeting therapies to treat human neurological disorders.RNA (New York, N.Y.) · 2023Article
- Counteracting the Common Shwachman-Diamond Syndrome-CausingInternational journal of molecular sciences · 2023Article
- Engineered U1 snRNAs to modulate alternatively spliced exons.Methods (San Diego, Calif.) · 2022Article
- Rescue of a familial dysautonomia mouse model by AAV9-Exon-specific U1 snRNA.American journal of human genetics · 2022Article
- OTC intron 4 variations mediate pathogenic splicing patterns caused by the c.386G>A mutation in humans and spfMolecular medicine (Cambridge, Mass.) · 2021Article
- Autosomal dominant optic atrophy: A novel treatment forMolecular therapy. Nucleic acids · 2021Article
- Dissection of pleiotropic effects of variants in and adjacent to F8 exon 19 and rescue of mRNA splicing and protein function.American journal of human genetics · 2021Article
- A deep learning approach to identify gene targets of a therapeutic for human splicing disorders.Nature communications · 2021Article
- Profiling of cis- and trans-acting factors supporting noncanonical splice site activation.RNA biology · 2021Article
- A Compensatory U1snRNA Partially Rescues FAH Splicing and Protein Expression in a Splicing-Defective Mouse Model of Tyrosinemia Type I.International journal of molecular sciences · 2020Article
- Innovative Therapeutic and Delivery Approaches Using Nanotechnology to Correct Splicing Defects Underlying Disease.Frontiers in genetics · 2020Review
- High-throughput analysis revealed mutations' diverging effects onRNA biology · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Exon-specific U1 snRNAs (ExSpe U1s) are modified U1 snRNAs that interact with intronic sequences downstream of the 5' splice site (ss) by complementarity. This process restores exon skipping caused by different types of mutation. We have investigated the molecular mechanism and activity of these molecules in spinal muscular atrophy (SMA), a genetic neuromuscular disease where a silent exonic transition on the survival motor neuron 2 (SMN2) leads to exon 7 (E7) skipping. By using different cellular models, we show that a single chromosome-integrated copy of ExSpe U1 induced a significant correction of endogenous SMN2 E7 splicing and resulted in the restoration of the corresponding SMN protein levels. Interestingly, the analysis of pre-mRNA transcript abundance and decay showed that ExSpe U1s promote E7 inclusion and stabilizes the SMN pre-mRNA intermediate. This selective effect on pre-mRNA stability resulted in higher levels of SMN mRNAs in comparison with those after treatment with an antisense oligonucleotide (AON) that targets corresponding intronic sequences. In mice harboring the SMN2 transgene, AAV-mediated delivery of ExSpe U1 increased E7 inclusion in brain, heart, liver, kidney, and skeletal muscle. The positive effect of ExSpe U1s on SMN pre-mRNA processing highlights their therapeutic potential in SMA and in other pathologies caused by exon-skipping mutations.
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Registered trials
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