prp8 mutations that cause human retinitis pigmentosa lead to a U5 snRNP maturation defect in yeast
| Autor: | Tatsiana Auchynnikava, Jean D. Beggs, Parastoo Ehsani, Richard J. Grainger, Kum-Loong Boon, Chris F. Inglehearn, J. David Barrass |
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| Rok vydání: | 2007 |
| Předmět: |
Saccharomyces cerevisiae Proteins
Macromolecular Substances Ribonucleoprotein U4-U6 Small Nuclear Recombinant Fusion Proteins Nuclear Localization Signals Saccharomyces cerevisiae Prp24 Protein degradation environment and public health Article Splicing factor Structural Biology Humans snRNP Nuclear protein Molecular Biology In Situ Hybridization Ribonucleoprotein U5 Small Nuclear biology Nuclear Proteins biology.organism_classification Molecular biology Cell biology Repressor Proteins Mutation Nuclear transport RNA Helicases Retinitis Pigmentosa Nuclear localization sequence |
| Zdroj: | Nature Structural & Molecular Biology. 14:1077-1083 |
| ISSN: | 1545-9985 1545-9993 |
| Popis: | Prp8 protein (Prp8p) is a highly conserved pre-mRNA splicing factor and a component of spliceosomal U5 small nuclear ribonucleoproteins (snRNPs). Although it is ubiquitously expressed, mutations in the C terminus of human Prp8p cause the retina-specific disease retinitis pigmentosa (RP). The biogenesis of U5 snRNPs is poorly characterized. We present evidence for a cytoplasmic precursor U5 snRNP in yeast that lacks the mature U5 snRNP component Brr2p and depends on a nuclear localization signal in Prp8p for its efficient nuclear import. The association of Brr2p with the U5 snRNP occurs within the nucleus. RP mutations in Prp8p in yeast result in nuclear accumulation of the precursor U5 snRNP, apparently as a consequence of disrupting the interaction of Prp8p with Brr2p. We therefore propose a novel assembly pathway for U5 snRNP complexes that is disrupted by mutations that cause human RP. |
| Databáze: | OpenAIRE |
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