Journal
JOURNAL OF NEUROSCIENCE
Volume 25, Issue 3, Pages 748-757Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2399-04.2005
Keywords
autosomal dominant retinitis pigmentosa (adRP); PRPF31; pre-mRNA splicing; retinal cells; apoptosis; rhodopsin
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Funding
- NCI NIH HHS [R01 CA114197-01A2, R01 CA114197] Funding Source: Medline
- NEI NIH HHS [R01 EY014576-04, EY08126, P30 EY008126, R01 EY014576] Funding Source: Medline
- NIA NIH HHS [R01 AG017518, R01 AG17518] Funding Source: Medline
- NIGMS NIH HHS [R01 GM070967-02, R01 GM070967] Funding Source: Medline
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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.
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