Article abstract
Nature Structural & Molecular Biology 14, 1077 - 1083 (2007)
Published online: 14 October 2007 | doi:10.1038/nsmb1303
prp8 mutations that cause human retinitis pigmentosa lead to a U5 snRNP maturation defect in yeast
Kum-Loong Boon1,3, Richard J Grainger1, Parastoo Ehsani1, J David Barrass1, Tatsiana Auchynnikava1, Chris F Inglehearn2 & Jean D Beggs1
Abstract
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.
- Wellcome Trust Centre for Cell Biology, University of Edinburgh, King's Buildings, Mayfield Road, Edinburgh EH9 3JR, UK.
- Section of Ophthalmology and Neuroscience, Leeds Institute of Molecular Medicine, University of Leeds, St. James's University Hospital, Beckett Street, Leeds LS9 7TF, UK.
- Present address: Center for Molecular Neurobiology, The Ohio State University, 132 Rightmire Hall, 1060 Carmack Road, Columbus, Ohio 43210, USA.
Correspondence to: Jean D Beggs1 e-mail: jbeggs@ed.ac.uk
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