prp8 mutations that cause human retinitis pigmentosa lead to a U5 snRNP maturation defect in yeast.

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.
Authors	Kum-Loong Boon, Richard J Grainger, Parastoo Ehsani, J David Barrass, Tatsiana Auchynnikava, Chris F Inglehearn, Jean D Beggs
Journal	Nature structural & molecular biology (Nat Struct Mol Biol) Vol. 14 Issue 11 Pg. 1077-83 (Nov 2007) ISSN: 1545-9985 [Electronic] United States
PMID	17934474 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Aar2p protein, S cerevisiae Macromolecular Substances Nuclear Localization Signals Nuclear Proteins PRP8 protein, S cerevisiae Recombinant Fusion Proteins Repressor Proteins Ribonucleoprotein, U4-U6 Small Nuclear Ribonucleoprotein, U5 Small Nuclear Saccharomyces cerevisiae Proteins BRR2 protein, S cerevisiae RNA Helicases
Topics	Humans In Situ Hybridization Macromolecular Substances (metabolism) Mutation Nuclear Localization Signals Nuclear Proteins (genetics, metabolism) RNA Helicases Recombinant Fusion Proteins (genetics, metabolism) Repressor Proteins (genetics, metabolism) Retinitis Pigmentosa (metabolism) Ribonucleoprotein, U4-U6 Small Nuclear Ribonucleoprotein, U5 Small Nuclear (genetics, metabolism) Saccharomyces cerevisiae (genetics, metabolism) Saccharomyces cerevisiae Proteins (chemistry, genetics, metabolism)

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