Disease mechanism for retinitis pigmentosa (RP11) caused by mutations in the splicing factor gene PRPF31

Deery, Evelyne and Vithana, Eranga N. and Newbold, Richard J. and Gallon, Victoria A. and Bhattacharya, Shomi S. and Warren, Martin J. and Hunt, David M. and Wilkie, Susan E. (2002) Disease mechanism for retinitis pigmentosa (RP11) caused by mutations in the splicing factor gene PRPF31. Human Molecular Genetics, 11 (25). pp. 3209-3219. ISSN 0964-6906. (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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This study investigates the functional consequences of two mutations, A194E and A216P, in the splicing factor gene PRPF31 linked to autosomal dominant retinitis pigmentosa (RP11). Using a yeast complementation assay, we demonstrate that introduction of the human A216P mutation into the yeast orthologue PRP31p results in only partial rescue of growth at the restrictive temperature, indicating that splicing function is not fully restored. An in vivo assay of splicing function in human cells using a bovine rod opsin splicing template did not detect any defect in splicing efficiency or accuracy attributable to either mutation, suggesting that neither has a dominant negative effect on splicing. However, western analysis and immunofluorescence microscopy of mammalian cells transfected with PRPF31 revealed that both mutations substantially hinder translocation of the protein into the nucleus. The overall effect may thus be an insufficiency in splicing function, which is revealed only under conditions of elevated splicing demand. With the need to replenish disc proteins on a daily basis, such conditions will exist in rod photoreceptors and this may underlie the disease pathology.

Item Type: Article
Additional information:
Uncontrolled keywords: Alternative Splicing/*genetics Amino Acid Sequence/genetics Animals COS Cells Cell Line Cercopithecus aethiops Eye Proteins/biosynthesis/*genetics Genetic Complementation Test Humans Molecular Sequence Data Mutagenesis, Site-Directed/genetics *Mutation, Missense Retinitis Pigmentosa/*genetics Saccharomyces cerevisiae/genetics Saccharomyces cerevisiae Proteins/genetics Transfection
Subjects: Q Science
Divisions: Faculties > Science Technology and Medical Studies > School of Biosciences
Depositing User: Martin Warren
Date Deposited: 12 Oct 2009 07:38
Last Modified: 16 May 2014 11:14
Resource URI: https://kar.kent.ac.uk/id/eprint/11061 (The current URI for this page, for reference purposes)
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