ArticleProceedings of the National Academy of Sciences of the United States of America2005
Reprogramming of tau alternative splicing by spliceosome-mediated RNA trans-splicing: implications for tauopathies.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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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.
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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
37 citing papers in PubMed, 59 citations in OpenAlex.
- Review
- Epitranscriptomic sculpting: the role of mMedical oncology (Northwood, London, England) · 2025Review
- Epigenetic Regulation and Therapeutic Targeting of Alternative Splicing Dysregulation in Cancer.Pharmaceuticals (Basel, Switzerland) · 2025Review
- RNA exon editing: Splicing the way to treat human diseases.Molecular therapy. Nucleic acids · 2024Review
- Alternative splicing in neurodegenerative disease and the promise of RNA therapies.Nature reviews. Neuroscience · 2023Review
- Elevated 4R-tau in astrocytes from asymptomatic carriers of the MAPT 10+16 intronic mutation.Journal of cellular and molecular medicine · 2022Article
- RNA-based therapeutics for neurological diseases.RNA biology · 2022Review
- SMaRT modulation of tau isoforms rescues cognitive and motor impairments in a preclinical model of tauopathy.Frontiers in bioengineering and biotechnology · 2022Article
- Alternative splicing in Alzheimer's disease.Aging clinical and experimental research · 2021Review
- Therapeutic applications of trans-splicing.British medical bulletin · 2020Article
- Targeting Alternative Splicing as a Potential Therapy for Episodic Ataxia Type 2.Biomedicines · 2020Review
- Innovative Therapeutic and Delivery Approaches Using Nanotechnology to Correct Splicing Defects Underlying Disease.Frontiers in genetics · 2020Review
- Molecular barcoding of viral vectors enables mapping and optimization of mRNARNA (New York, N.Y.) · 2018Article
- Review
- Tau Isoforms Imbalance Impairs the Axonal Transport of the Amyloid Precursor Protein in Human Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Construction and validation of an RNA trans-splicing molecule suitable to repair a large number of COL7A1 mutations.Gene therapy · 2016Article
- mRNA trans-splicing in gene therapy for genetic diseases.Wiley interdisciplinary reviews. RNA · 2016Review
- Developmental regulation of tau splicing is disrupted in stem cell-derived neurons from frontotemporal dementia patients with the 10 + 16 splice-site mutation in MAPT.Human molecular genetics · 2015Article
- Repair of rhodopsin mRNA by spliceosome-mediated RNA trans-splicing: a new approach for autosomal dominant retinitis pigmentosa.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Article
- Cis-splicing and translation of the pre-trans-splicing molecule combine with efficiency in spliceosome-mediated RNA trans-splicing.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) is caused by mutations in the gene encoding the microtubule-associated protein, tau. Some FTDP-17 mutations affect exon 10 splicing. To correct aberrant exon 10 splicing while retaining endogenous transcriptional control, we evaluated the feasibility of using spliceosome-mediated RNA trans-splicing (SMaRT) to reprogram tau mRNA. We designed a pre-trans-splicing molecule containing human tau exons 10 to 13 and a binding domain complementary to the 3' end of tau intron 9. A minigene comprising tau exons 9, 10, and 11 and minimal flanking intronic sequences was used as a target. RT-PCR analysis of SH-SY5Y cells or COS cells cotransfected with a minigene and a pre-trans-splicing molecule using primers to opposite sides of the predicted splice junction generated products containing exons 9 to 13. Sequencing of the chimeric products showed that an exact exon 9-exon 10 junction had been created, thus demonstrating that tau RNA can be reprogrammed by trans-splicing. Furthermore, by using the same paradigm with a minigene containing full-length intronic sequences, we show that cis-splicing exclusion of exon 10 can be by-passed by trans-splicing and that conversion of exon 10(-) tau RNA into exon 10(+) tau RNA could be achieved with approximately 34% efficiency. Our results demonstrate that an alternatively spliced exon can be replaced by trans-splicing and open the way to novel therapeutic applications of SMaRT for tauopathies and other disorders linked to aberrant alternative splicing.
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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.