ArticleNature communications2024
PRPF8-mediated dysregulation of hBrr2 helicase disrupts human spliceosome kinetics and 5´-splice-site selection causing tissue-specific defects.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 14 citations in OpenAlex.
- Cell-autonomous restoration of splicing homeostasis and RP11 phenotype in patient-derived RPE and retinal organoids by PRPF31.AAV gene therapy.Nature communications · 2026Article
- Neurochondrin promotes U5 snRNP maturation by regulating AAR2 release from PRPF8.Nucleic acids research · 2026Article
- PRPF8-associated retinitis pigmentosa variant induces human neural retina-autonomous photoreceptor defects.Scientific reports · 2026Article
- PRPF8 Mutation-Induced Defects in Human iPSC-Derived RPE Are Rescued by Adenine Base Editing.Investigative ophthalmology & visual science · 2026Article
- Neurodegenerative spliceosomopathies.Frontiers in cell and developmental biology · 2026Review
- Generation and Characterization of Patient-Derived Human Pluripotent Stem Cell Lines for Retinal Gene Therapy.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Decoding retinitis pigmentosa: molecular targets and therapy with focus on pre-mRNA splicing.Cellular and molecular life sciences : CMLS · 2025Review
- Alternative Splicing Dysregulation in Retinitis Pigmentosa: Pathogenic Mechanisms and Therapeutic Opportunities.Biomolecules · 2025Review
- Single-Cell Transcriptomics in Inherited Retinal Dystrophies: Current Findings and Emerging Perspectives.Genes · 2025Review
- The RNA splicing factor PRPF8 is required for left-right organiser cilia differentiation and determination of cardiac left-right asymmetry via regulation ofbioRxiv : the preprint server for biology · 2025Article
- Reporting a Homozygous Case of Neurodevelopmental Disorder Associated With a Novel PRPF8 Variant.Molecular genetics & genomic medicine · 2025Article
- Research Progress on the Relationship Between PRPF8 and Cancer.Current issues in molecular biology · 2025Review
- Genetic relationship between Sjögren's syndrome and abdominal aortic aneurysm: insights from a European population's genome-wide association analysis.Frontiers in cardiovascular medicine · 2025Article
- Addressing the tissue specificity of U5 snRNP spliceosomopathies.Frontiers in cell and developmental biology · 2025Article
- Optimized Prime Editing of Human Induced Pluripotent Stem Cells to Efficiently Generate Isogenic Models of Mendelian Diseases.International journal of molecular sciences · 2024Article
- Transcriptomic Alterations in Spliceosome Components in Advanced Heart Failure: Status of Cardiac-Specific Alternative Splicing Factors.International journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
32 authors at 10 institutions in 5 countries.
Funding
Abstract
The carboxy-terminus of the spliceosomal protein PRPF8, which regulates the RNA helicase Brr2, is a hotspot for mutations causing retinitis pigmentosa-type 13, with unclear role in human splicing and tissue-specificity mechanism. We used patient induced pluripotent stem cells-derived cells, carrying the heterozygous PRPF8 c.6926 A > C (p.H2309P) mutation to demonstrate retinal-specific endophenotypes comprising photoreceptor loss, apical-basal polarity and ciliary defects. Comprehensive molecular, transcriptomic, and proteomic analyses revealed a role of the PRPF8/Brr2 regulation in 5'-splice site (5'SS) selection by spliceosomes, for which disruption impaired alternative splicing and weak/suboptimal 5'SS selection, and enhanced cryptic splicing, predominantly in ciliary and retinal-specific transcripts. Altered splicing efficiency, nuclear speckles organisation, and PRPF8 interaction with U6 snRNA, caused accumulation of active spliceosomes and poly(A)+ mRNAs in unique splicing clusters located at the nuclear periphery of photoreceptors. Collectively these elucidate the role of PRPF8/Brr2 regulatory mechanisms in splicing and the molecular basis of retinal disease, informing therapeutic approaches.
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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 Socratic graph.