ArticleCell2018
Defects in the Alternative Splicing-Dependent Regulation of REST Cause Deafness.
Article in Cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
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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
51 citing papers in PubMed, 78 citations in OpenAlex.
- CASZ1 regulates the maturation of outer hair cells and is required for hearing in mice.iScience · 2026Article
- Novel Pathogenic Variant Confirms the Association of REST and Jones Syndrome.Clinical genetics · 2026Article
- Regulated microexon alternative splicing in single neurons tunes synaptic function.EMBO reports · 2025Article
- Epigenetic Modifications in Sensorineural Hearing Loss: Protective Mechanisms and Therapeutic Potential.Current medical science · 2025Review
- Novel genetic determinants contribute to hearing loss in a central European cohort with enlarged vestibular aqueduct.Molecular medicine (Cambridge, Mass.) · 2025Article
- The Complexity of Familial Inheritance in Pectus Excavatum: A Ten-Family Exome Sequencing Analysis.Genes · 2024Article
- Splice-switching antisense oligonucleotide controlling tumor suppressor REST is a novel therapeutic medicine for neuroendocrine cancer.Molecular therapy. Nucleic acids · 2024Article
- High-throughput sensitive screening of small molecule modulators of microexon alternative splicing using dual Nano and Firefly luciferase reporters.Nature communications · 2024Article
- FAK-LINC01089 negative regulatory loop controls chemoresistance and progression of small cell lung cancer.Oncogene · 2024Article
- Unique transcriptomes of sensory and non-sensory neurons: insights from Splicing Regulatory States.Molecular systems biology · 2024Review
- Suberoylanilide Hydroxamic Acid (SAHA) Is a Driver Molecule of Neuroplasticity: Implication for Neurological Diseases.Biomolecules · 2023Review
- Article
- Autosomal Dominant Non-Syndromic Hearing Loss (DFNA): A Comprehensive Narrative Review.Biomedicines · 2023Review
- Tissue-specific regulation of gene expression via unproductive splicing.Nucleic acids research · 2023Article
- Pathogenic REST variant causing Jones syndrome and a review of the literature.European journal of human genetics : EJHG · 2023Review
- The cause of Jones syndrome put to REST: a mutation in the REST gene causes gingival fibromatosis and hearing loss.European journal of human genetics : EJHG · 2023Article
- EpiFactors 2022: expansion and enhancement of a curated database of human epigenetic factors and complexes.Nucleic acids research · 2023Article
- Protein Expression of NEK2, JMJD4, and REST in Clear Cell Renal Cell Carcinoma (ccRCC): Clinical, Pathological, and Prognostic Findings.Iranian journal of pathology · 2023Article
- Alternative splicing in shaping the molecular landscape of the cochlea.Frontiers in cell and developmental biology · 2023Review
- Emerging Roles of RNA-Binding Proteins in Inner Ear Hair Cell Development and Regeneration.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
The DNA-binding protein REST forms complexes with histone deacetylases (HDACs) to repress neuronal genes in non-neuronal cells. In differentiating neurons, REST is downregulated predominantly by transcriptional silencing. Here we report that post-transcriptional inactivation of REST by alternative splicing is required for hearing in humans and mice. We show that, in the mechanosensory hair cells of the mouse ear, regulated alternative splicing of a frameshift-causing exon into the Rest mRNA is essential for the derepression of many neuronal genes. Heterozygous deletion of this alternative exon of mouse Rest causes hair cell degeneration and deafness, and the HDAC inhibitor SAHA (Vorinostat) rescues the hearing of these mice. In humans, inhibition of the frameshifting splicing event by a novel REST variant is associated with dominantly inherited deafness. Our data reveal the necessity for alternative splicing-dependent regulation of REST in hair cells, and they identify a potential treatment for a group of hereditary deafness cases.
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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.