ArticleJournal of molecular medicine (Berlin, Germany)2007
Therapeutic potential and mechanism of kinetin as a treatment for the human splicing disease familial dysautonomia.
Article in Journal of molecular medicine (Berlin, Germany), 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 73 citations in OpenAlex.
- AAV2-mediated intravitreal delivery of exon-specific U1 snRNA rescues optic neuropathy in familial dysautonomia.Molecular therapy. Nucleic acids · 2026Article
- Article
- Modulation of prion protein expression through cryptic splice site manipulation.bioRxiv : the preprint server for biology · 2023Article
- Regulation of pre-mRNA splicing: roles in physiology and disease, and therapeutic prospects.Nature reviews. Genetics · 2023Review
- Development of an oral treatment that rescues gait ataxia and retinal degeneration in a phenotypic mouse model of familial dysautonomia.American journal of human genetics · 2023Article
- Preclinical development of kinetin as a safe error-prone SARS-CoV-2 antiviral able to attenuate virus-induced inflammation.Nature communications · 2023Article
- On the human health benefits of microalgal phytohormones: An explorativeComputational and structural biotechnology journal · 2023Article
- Cytokinins: Wide-Spread Signaling Hormones from Plants to Humans with High Medical Potential.Nutrients · 2022Review
- Article
- A deep learning approach to identify gene targets of a therapeutic for human splicing disorders.Nature communications · 2021Article
- RNA-Targeting Splicing Modifiers: Drug Development and Screening Assays.Molecules (Basel, Switzerland) · 2021Review
- Modulatory and Toxicological Perspectives on the Effects of the Small Molecule Kinetin.Molecules (Basel, Switzerland) · 2021Article
- Hereditary Sensory and Autonomic Neuropathies: Adding More to the Classification.Current neurology and neuroscience reports · 2019Review
- ELP1 Splicing Correction Reverses Proprioceptive Sensory Loss in Familial Dysautonomia.American journal of human genetics · 2019Article
- Blocking of an intronic splicing silencer completely rescues IKBKAP exon 20 splicing in familial dysautonomia patient cells.Nucleic acids research · 2018Article
- Exon-specific U1 snRNAs improve ELP1 exon 20 definition and rescue ELP1 protein expression in a familial dysautonomia mouse model.Human molecular genetics · 2018Article
- Orthostatic hypotension: does the heart rate matter? And other updates on recent autonomic research.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2018Article
- Antisense oligonucleotides correct the familial dysautonomia splicing defect in IKBKAP transgenic mice.Nucleic acids research · 2018Article
- RBM24 promotes U1 snRNP recognition of the mutated 5' splice site in theRNA (New York, N.Y.) · 2017Article
- Phosphatidylserine Ameliorates Neurodegenerative Symptoms and Enhances Axonal Transport in a Mouse Model of Familial Dysautonomia.PLoS genetics · 2016Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations that affect the splicing of pre-mRNA are a major cause of human disease. Familial dysautonomia (FD) is a recessive neurodegenerative disease caused by a T to C transition at base pair 6 of IKBKAP intron 20. This mutation results in variable tissue-specific skipping of exon 20. Previously, we reported that the plant cytokinin kinetin dramatically increases exon 20 inclusion in RNA isolated from cultured FD cells. The goal of the current study was to investigate the nature of the FD splicing defect and the mechanism by which kinetin improves exon inclusion, as such knowledge will facilitate the development of future therapeutics aimed at regulating mRNA splicing. In this study, we demonstrate that treatment of FD lymphoblast cell lines with kinetin increases IKBKAP mRNA and IKAP protein to normal levels. Using a series of minigene constructs, we show that deletion of a region at the end of IKBKAP exon 20 disrupts the ability of kinetin to improve exon inclusion, pinpointing a kinetin responsive sequence element. We next performed a screen of endogenously expressed genes with multiple isoforms resulting from exon skipping events and show that kinetin's ability to improve exon inclusion is not limited to IKBKAP. Lastly, we highlight the potential of kinetin for the treatment of other human splicing disorders by showing correction of a splicing defect in neurofibromatosis.
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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.