Mutations in PRPF31 Inhibit Pre-mRNA Splicing of Rhodopsin Gene and Cause Apoptosis of Retinal Cells

Mutations in human PRPF31 gene have been identified in patients with autosomal dominant retinitis pigmentosa (adRP). To begin to understand mechanisms by which defects in this general splicing factor cause retinal degeneration, we examined the relationship between PRPF31 and pre-mRNA splicing of photoreceptor-specific genes. We used a specific anti-PRPF31 antibody to immunoprecipitate splicing complexes from retinal cells and identified the transcript of rhodopsin gene (RHO) among RNA species associated with PRPF31-containing complexes. Mutant PRPF31 proteins significantly inhibited pre-mRNA splicing of intron 3 in RHO gene. In primary retinal cell cultures, expression of the mutant PRPF31 proteins reduced rhodopsin expression and caused apoptosis of rhodopsin-positive retinal cells. This primary retinal culture assay provides an in vitro model to study photoreceptor cell death caused by PRPF31 mutations. Our results demonstrate that mutations in PRPF31 gene affect RHO pre-mRNA splicing and reveal a link between PRPF31 and RHO, two major adRP genes.

• Publication year

  2005

• Venue

  Journal of Neuroscience

• Publication date

  2005-01-19

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1523/JNEUROSCI.2399-04.2005PMID 15659613PMCID PMC2149905
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Encyclopedia of molecular cell biology and molecular medicine

  2014cited by this paper
• Alternatively Spliced Genes

  2006cited by this paper
• Pre-mRNA splicing and human disease.

  2003cited by this paper
• Alternative pre-mRNA splicing and regulation of programmed cell death.

  2003cited by this paper
• Retinitis pigmentosa: genes, proteins and prospects.

  2003cited by this paper
• Progress toward understanding the genetic and biochemical mechanisms of inherited photoreceptor degenerations.

  2003cited by this paper
• Encyclopedia of Molecular Cell Biology and Molecular Medicine

  2003cited by this paper
• Disease mechanism for retinitis pigmentosa (RP11) caused by mutations in the splicing factor gene PRPF31.

  2002cited by this paper
• Mutations in HPRP3, a third member of pre-mRNA splicing factor genes, implicated in autosomal dominant retinitis pigmentosa.

  2002cited by this paper
• Clinical characterization, linkage analysis, and PRPC8 mutation analysis of a family with autosomal dominant retinitis pigmentosa type 13 (RP13)

  2002cited by this paper
• Transcriptome analysis of the retina

  2002cited by this paper
• Retinal prosthesis for the blind.

  2002cited by this paper
• Gene therapy for genetic and acquired retinal diseases.

  2002cited by this paper
• Transplantation of intact sheets of fetal neural retina with its retinal pigment epithelium in retinitis pigmentosa patients.

  2002cited by this paper
• On the genetics of retinitis pigmentosa and on mutation‐independent approaches to therapeutic intervention

  2002cited by this paper
• Retinitis pigmentosa and allied diseases: numerous diseases, genes, and inheritance patterns.

  2002cited by this paper
• The SMN complex, an assemblyosome of ribonucleoproteins.

  2002cited by this paper
• Comprehensive proteomic analysis of the human spliceosome

  2002cited by this paper
• Small Nuclear Ribonucleoprotein Remodeling During Catalytic Activation of the Spliceosome

  2002cited by this paper
• Protein 61K, encoded by a gene (PRPF31) linked to autosomal dominant retinitis pigmentosa, is required for U4/U6·U5 tri‐snRNP formation and pre‐mRNA splicing

  2002cited by this paper
• The splice of life: Alternative splicing and neurological disease

  2001cited by this paper
• Mutations in the pre-mRNA splicing factor gene PRPC8 in autosomal dominant retinitis pigmentosa (RP13).

  2001cited by this paper
• Selective excitotoxic degeneration of adult pig retinal ganglion cells in vitro.

  2001cited by this paper
• Pre-mRNA splicing in the new millennium.

  2001cited by this paper
• RP11 and RP13: unexpected gene loci.

  2001cited by this paper
• Alternative RNA splicing in the nervous system.

  2001cited by this paper
• Caspase-2 pre-mRNA alternative splicing: Identification of an intronic element containing a decoy 3' acceptor site.

  2001cited by this paper
• A human homolog of yeast pre-mRNA splicing gene, PRP31, underlies autosomal dominant retinitis pigmentosa on chromosome 19q13.4 (RP11).

  2001influential reference
• Gene therapy and retinitis pigmentosa: advances and future challenges

  2001influential reference
• Ribozyme rescue of photoreceptor cells in P23H transgenic rats: long-term survival and late-stage therapy.

  2000cited by this paper
• Novel rhodopsin mutations Gly114Val and Gln184Pro in dominant retinitis pigmentosa.

  2000cited by this paper
• Selective transplantation of rods delays cone loss in a retinitis pigmentosa model.

  2000cited by this paper
• Aberrant Splicing of tau Pre-mRNA Caused by Intronic Mutations Associated with the Inherited Dementia Frontotemporal Dementia with Parkinsonism Linked to Chromosome 17

  2000cited by this paper
• A brief review of retinitis pigmentosa and the identified retinitis pigmentosa genes.

  2000cited by this paper
• Gene therapy for retinitis pigmentosa.

  2000cited by this paper
• Isolation of an essential Schizosaccharomyces pombe gene, prp31(+), that links splicing and meiosis.

  2000cited by this paper
• Directional guidance of neuronal migration in the olfactory system by the protein Slit

  1999cited by this paper
• Vertebrate slit, a secreted ligand for the transmembrane protein roundabout, is a repellent for olfactory bulb axons.

  1999cited by this paper
• Regulation of Ich-1 pre-mRNA alternative splicing and apoptosis by mammalian splicing factors.

  1998cited by this paper
• Molecular genetics of human retinal dystrophies

  1998cited by this paper
• RP11 is the second most common locus for dominant retinitis pigmentosa.

  1998cited by this paper
• Retinopathy induced in mice by targeted disruption of the rhodopsin gene

  1997cited by this paper
• Prp31p promotes the association of the U4/U6 x U5 tri-snRNP with prespliceosomes to form spliceosomes in Saccharomyces cerevisiae

  1997cited by this paper
• The yeast Prp3 protein is a U4/U6 snRNP protein necessary for integrity of the U4/U6 snRNP and the U4/U6.U5 tri-snRNP.

  1997cited by this paper
• Evidence for a major retinitis pigmentosa locus on 19q13.4 (RP11) and association with a unique bimodal expressivity phenotype.

  1996cited by this paper
• The PRP31 gene encodes a novel protein required for pre-mRNA splicing in Saccharomyces cerevisiae.

  1996cited by this paper
• Six novel genes necessary for pre-mRNA splicing in Saccharomyces cerevisiae.

  1996cited by this paper
• Bimodal expressivity in dominant retinitis pigmentosa genetically linked to chromosome 19q.

  1995cited by this paper
• Further screening of the rhodopsin gene in patients with autosomal dominant retinitis pigmentosa.

  1994cited by this paper
• Apoptosis: Final common pathway of photoreceptor death in rd, rds, and mutant mice

  1993cited by this paper
• Apoptosis: final common pathway of photoreceptor death in rd, rds, and rhodopsin mutant mice.

  1993cited by this paper
• Autosomal dominant retinitis pigmentosa with apparent incomplete penetrance: a clinical, electrophysiological, psychophysical, and molecular genetic study.

  1993influential reference
• RNA world

  1987cited by this paper

• Decoding retinitis pigmentosa: molecular targets and therapy with focus on pre-mRNA splicing

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• Pluripotent stem cell-derived models of retinal disease: Elucidating pathogenesis, evaluating novel treatments, and estimating toxicity.

  2024cites this paper
• Cellular and Molecular Mechanisms of Pathogenesis Underlying Inherited Retinal Dystrophies

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• PRPF31-retinitis pigmentosa: Challenges and opportunities for clinical translation.

  2023cites this paper
• Retinitis pigmentosa–associated mutations in mouse Prpf8 cause misexpression of circRNAs and degeneration of cerebellar granule cells

  2023cites this paper
• Retinitis Pigmentosa: Progress in Molecular Pathology and Biotherapeutical Strategies

  2022cites this paper
• Retinitis pigmentosa associated mutations in mouse Prpf8 cause misexpression of circRNAs and degeneration of cerebellar granule neurons

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• Gene augmentation prevents retinal degeneration in a CRISPR/Cas9-based mouse model of PRPF31 retinitis pigmentosa

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• Microtubule modification defects underlie cilium degeneration in cell models of retinitis pigmentosa associated with pre-mRNA splicing factor mutations

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• PRPF31 interacts with PRPH2 confirmed by co-immunoprecipitation and co-localization

  2022cites this paper
• Correction: Retinitis pigmentosa-linked mutation in DHX38 modulates its splicing activity

  2022influential citation
• Mutations in the splicing regulator Prp31 lead to retinal degeneration in Drosophila

  2021cites this paper
• Pre-mRNA Processing Factors and Retinitis Pigmentosa: RNA Splicing and Beyond

  2021influential citation
• Prpf31 is essential for the survival and differentiation of retinal progenitor cells by modulating alternative splicing

  2021cites this paper
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  2020cites this paper
• Identification of two novel PRPF31 mutations in Chinese families with non‐syndromic autosomal dominant retinitis pigmentosa

  2020cites this paper
• Mutation spectrum of PRPF31, genotype-phenotype correlation in retinitis pigmentosa, and opportunities for therapy

  2020cites this paper
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  2020cites this paper
• AAV-Mediated Gene Augmentation Therapy Restores Critical Functions in Mutant PRPF31+/− iPSC-Derived RPE Cells

  2019cites this paper
• Differential stability of variant OPN1LW gene transcripts in myopic patients

  2019cites this paper
• Retinal Pigment Epithelial Cells: The Unveiled Component in the Etiology of Prpf Splicing Factor-Associated Retinitis Pigmentosa.

  2019cites this paper
• Retinal pigment epithelium degeneration caused by aggregation of PRPF31 and the role of HSP70 family of proteins

  2019cites this paper
• JCB_201701165 1..18

  2018influential citation
• The splicing regulator Prp31 prevents retinal degeneration in Drosophila by regulating Rhodopsin levels

  2018cites this paper
• A novel mutation in the PRPF31 in a North Indian adRP family with incomplete penetrance

  2018cites this paper
• Long-term clinical course of 2 Japanese patients with PRPF31-related retinitis pigmentosa

  2018cites this paper
• A Combined in silico, in vitro and Clinical Approach to Characterize Novel Pathogenic Missense Variants in PRPF31 in Retinitis Pigmentosa

  2018cites this paper
• Targeted RP9 ablation and mutagenesis in mouse photoreceptor cells by CRISPR-Cas9

  2017cites this paper
• Human iPSC-derived RPE and retinal organoids reveal impaired alternative splicing of genes involved in pre-mRNA splicing in PRPF31 autosomal dominant retinitis pigmentosa

  2017cites this paper
• Assembly of the U5 snRNP component PRPF8 is controlled by the HSP90/R2TP chaperones

  2017influential citation
• Molecular genetics and emerging therapies for retinitis pigmentosa: Basic research and clinical perspectives.

  2017cites this paper
• JCB_201701165 1579..1596

  2017influential citation
• Mutations in the Drosophila splicing regulator Prp31 as a model for Retinitis pigmentosa 11

  2017influential citation
• Identification of Genetic Variants in PDC, RHO, PDE6A and PDE6B in Dogs with Progressive Retinal Atrophy

  2016cites this paper
• Identification of an Alternative Splicing Product of the Otx2 Gene Expressed in the Neural Retina and Retinal Pigmented Epithelial Cells

  2016cites this paper
• mRNA metabolism and neuronal disease

  2015cites this paper
• The diagnostic application of targeted re-sequencing in Korean patients with retinitis pigmentosa

  2015cites this paper
• Efficient Gene Transfer in Chick Retinas for Primary Cell Culture Studies: An Ex-ovo Electroporation Approach.

  2015cites this paper
• Retinal dystrophies, genomic applications in diagnosis and prospects for therapy.

  2015influential citation
• PRPF4 mutations cause autosomal dominant retinitis pigmentosa.

  2014cites this paper
• Mutation analysis of pre-mRNA splicing genes in Chinese families with retinitis pigmentosa

  2014cites this paper
• Aberrant splicing in neurological diseases

  2013cites this paper
• Ex vivo electroporation of retinal cells: a novel, high efficiency method for functional studies in primary retinal cultures.

  2013cites this paper
• Rhodopsin F45L Allele Does Not Cause Autosomal Dominant Retinitis Pigmentosa in a Large Caucasian Family.

  2013cites this paper
• Alternative splicing and retinal degeneration

  2013cites this paper
• Rhodopsin homeostasis and retinal degeneration: lessons from the fly.

  2013cites this paper
• The Role of Stat3 in Mouse Models of Inherited Photoreceptor Degeneration

  2013cites this paper
• Regulation of in the context of cell nucleus

  2011cites this paper
• Mutant Prpf31 causes pre-mRNA splicing defects and rod photoreceptor cell degeneration in a zebrafish model for Retinitis pigmentosa

  2011influential citation
• Identification of compound heterozygous mutations in GNPTG in three siblings of a Chinese family with mucolipidosis type III gamma.

  2011cites this paper
• PRPF mutations are associated with generalized defects in spliceosome formation and pre-mRNA splicing in patients with retinitis pigmentosa.

  2011cites this paper
• Regulation of Tumorigenic Spliced Isoforms in Cancer

  2011cites this paper
• Dynamic usage of alternative splicing exons during mouse retina development

  2011cites this paper
• Three gene-targeted mouse models of RNA splicing factor RP show late-onset RPE and retinal degeneration.

  2011cites this paper
• The splicing factor Prp31 is essential for photoreceptor development in Drosophila

  2010cites this paper
• The molecular basis of human retinal and vitreoretinal diseases.

  2010influential citation
• Prevalence and novelty of PRPF31 mutations in French autosomal dominant rod-cone dystrophy patients and a review of published reports

  2010cites this paper
• Study of gene-targeted mouse models of splicing factor gene Prpf31 implicated in human autosomal dominant retinitis pigmentosa (RP).

  2009cites this paper
• A mutation linked to retinitis pigmentosa in HPRP31 causes protein instability and impairs its interactions with spliceosomal snRNPs.

  2009cites this paper
• Identification of a novel splicing mutation in the growth hormone (GH)-releasing hormone receptor gene in a Chinese family with pituitary dwarfism.

  2009cites this paper
• Evaluation of splicing efficiency in lymphoblastoid cell lines from patients with splicing-factor retinitis pigmentosa

  2008cites this paper
• A Targeted Deleterious Allele of the Splicing Factor SCNM1 in the Mouse

  2008cites this paper
• Decreased levels of the RNA splicing factor Prpf3 in mice and zebrafish do not cause photoreceptor degeneration.

  2008cites this paper
• Disease mechanism for retinitis pigmentosa (RP11) caused by missense mutations in the splicing factor gene PRPF31

  2008influential citation
• Transcriptional expression of cis‐acting and trans‐acting splicing mutations cause autosomal dominant retinitis pigmentosa

  2008cites this paper
• Premature termination codons in PRPF31 cause retinitis pigmentosa via haploinsufficiency due to nonsense-mediated mRNA decay.

  2008cites this paper
• Identification of photoreceptor genes affected by PRPF31 mutations associated with autosomal dominant retinitis pigmentosa.

  2007cites this paper
• Pre-mRNA splicing and retinitis pigmentosa.

  2006cites this paper
• Pre-mRNA Splicing in Eukaryotic Cells

  2006cites this paper
• Variation in retinitis pigmentosa‐11 (PRPF31 or RP11) gene expression between symptomatic and asymptomatic patients with dominant RP11 mutations

  2006cites this paper
• A study of the nuclear trafficking of the splicing factor protein PRPF31 linked to autosomal dominant retinitis pigmentosa (ADRP).

  2005cites this paper
• The splicing machinery is a genetic modifier of disease severity.

  2005cites this paper
• Analysis of yeast Prp8 protein and its role in U5 snRNP assembly

  2005cites this paper