ArticleProceedings of the National Academy of Sciences of the United States of America2015
Rectifier of aberrant mRNA splicing recovers tRNA modification in familial dysautonomia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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68 citing papers in PubMed, 113 citations in OpenAlex.
- Depleting prion protein using splice-switching small molecules.bioRxiv : the preprint server for biology · 2026Article
- Pre-mRNA splicing regulates cellular dedifferentiation via lipid metabolism in a cytokinin-dependent manner in Arabidopsis.Plant physiology · 2026Article
- Translational regulation by oxidative desulfuration of tRNA modifications.Nature communications · 2026Article
- Utilization of Induced Pluripotent Stem Cell-Derived Neurons to Investigate the Splice-Modification Efficacy of Splice-Switching Drug Candidates.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Uridines Modified with Sulfur or Selenium in U-G Wobble Pairs Matter for tRNA Function.Current medicinal chemistry · 2026Review
- tRNA Modifications: A Tale of Two Viruses-SARS-CoV-2 and ZIKV.International journal of molecular sciences · 2025Article
- tRNA modifications tune mCell · 2025Article
- Invention of an oral medication for cardiac Fabry disease caused by RNA mis-splicing.Science advances · 2025Article
- A tRNA modification with aminovaleramide facilitates AUA decoding in protein synthesis.Nature chemical biology · 2025Article
- NAIL-MS reveals tRNA and rRNA hypomodification as a consequence of 5-fluorouracil treatment.Nucleic acids research · 2025Article
- Optimization of 2',4'-BNA/LNA-Based Oligonucleotides for Splicing Modulation in Vitro.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Specificity, synergy, and mechanisms of splice-modifying drugs.Nature communications · 2024Article
- Branchpoints as potential targets of exon-skipping therapies for genetic disorders.Molecular therapy. Nucleic acids · 2023Article
- A homozygous mutation in the human selenocysteine tRNA gene impairs UGA recoding activity and selenoproteome regulation by selenium.Nucleic acids research · 2023Article
- The nexus between RNA-binding proteins and their effectors.Nature reviews. Genetics · 2023Review
- 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
- Recent advances in the molecular understanding of medulloblastoma.Cancer science · 2023Review
- E2/E3-independent ubiquitin-like protein conjugation by Urm1 is directly coupled to cysteine persulfidation.The EMBO journal · 2022Article
- CHIKV infection reprograms codon optimality to favor viral RNA translation by altering the tRNA epitranscriptome.Nature communications · 2022Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Familial dysautonomia (FD), a hereditary sensory and autonomic neuropathy, is caused by missplicing of exon 20, resulting from an intronic mutation in the inhibitor of kappa light polypeptide gene enhancer in B cells, kinase complex-associated protein (IKBKAP) gene encoding IKK complex-associated protein (IKAP)/elongator protein 1 (ELP1). A newly established splicing reporter assay allowed us to visualize pathogenic splicing in cells and to screen small chemicals for the ability to correct the aberrant splicing of IKBKAP. Using this splicing reporter, we screened our chemical libraries and identified a compound, rectifier of aberrant splicing (RECTAS), that rectifies the aberrant IKBKAP splicing in cells from patients with FD. Here, we found that the levels of modified uridine at the wobble position in cytoplasmic tRNAs are reduced in cells from patients with FD and that treatment with RECTAS increases the expression of IKAP and recovers the tRNA modifications. These findings suggest that the missplicing of IKBKAP results in reduced tRNA modifications in patients with FD and that RECTAS is a promising therapeutic drug candidate for FD.
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