ArticleHuman molecular genetics2009
Correction of tau mis-splicing caused by FTDP-17 MAPT mutations by spliceosome-mediated RNA trans-splicing.
Article in Human molecular genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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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
32 citing papers in PubMed, 54 citations in OpenAlex.
- Review
- Unravelling the Proteinopathic Engagement of α-Synuclein, Tau, and Amyloid Beta in Parkinson's Disease: Mitochondrial Collapse as a Pivotal Driver of Neurodegeneration.Neurochemical research · 2025Review
- Transgenic iPSC Lines with Genetically Encoded MitoTimer to Study Mitochondrial Biogenesis in Dopaminergic Neurons with Tauopathy.Biomedicines · 2025Article
- Exploring the therapeutic potential of modulating nonsense-mediated mRNA decay.RNA (New York, N.Y.) · 2025Review
- Protein isoform-centric therapeutics: expanding targets and increasing specificity.Nature reviews. Drug discovery · 2024Review
- Therapeutic targeting of RNA for neurological and neuromuscular disease.Genes & development · 2024Review
- 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
- 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
- Experimental Disease-Modifying Agents for Frontotemporal Lobar Degeneration.Journal of experimental pharmacology · 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
- Efficient system for upstream mRNA trans-splicing to generate covalent, head-to-tail, protein multimers.Scientific reports · 2019Article
- A walk through tau therapeutic strategies.Acta neuropathologica communications · 2019Review
- Centronuclear myopathies under attack: A plethora of therapeutic targets.Journal of neuromuscular diseases · 2018Review
- 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
- Mechanical Stress and Single Nucleotide Variants Regulate Alternative Splicing of the MYLK Gene.American journal of respiratory cell and molecular biology · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) is caused by mutations in the MAPT gene, encoding the tau protein that accumulates in intraneuronal lesions in a number of neurodegenerative diseases. Several FTDP-17 mutations affect alternative splicing and result in excess exon 10 (E10) inclusion in tau mRNA. RNA reprogramming using spliceosome-mediated RNA trans-splicing (SMaRT) could be a method of choice to correct aberrant E10 splicing resulting from FTDP-17 mutations. SMaRT creates a hybrid mRNA through a trans-splicing reaction between an endogenous target pre-mRNA and a pre-trans-splicing RNA molecule (PTM). However, FTDP-17 mutations affect the strength of cis-splicing elements and could favor cis-splicing over trans-splicing. Excess E10 inclusion in FTDP-17 can be caused by intronic mutations destabilizing a stem-loop protecting the 5' splice site at the E10/intron 10 junction. COS cells transfected with a minigene containing the intronic +14 mutation produce exclusively E10(+) RNA. Generation of E10(-) RNA was restored after co-transfection with a PTM designed to exclude E10. Similar results were obtained with a target containing the exonic N279K mutation which strengthens a splicing enhancer within E10. Conversely, increase or decrease in E10 content was achieved by trans-splicing from a target carrying the Delta280K mutation, which weakens the same splicing enhancer. Thus E10 inclusion can be modulated by trans-splicing irrespective of the strength of the cis-splicing elements affected by FTDP-17 mutations. In conclusion, RNA trans-splicing could provide the basis of therapeutic strategies for impaired alternative splicing caused by pathogenic mutations in cis-acting splicing elements.
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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.