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

被引:81
作者
Boon, Kum-Loong
Grainger, Richard J.
Ehsani, Parastoo
Barrass, J. David
Auchynnikava, Tatsiana
Inglehearn, Chris F.
Beggs, Jean D.
机构
[1] Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland
[2] Univ Leeds, St James Univ Hosp, Leeds Inst Mol Med, Sect Ophthalmol & Neurosci, Leeds LS9 7TF, W Yorkshire, England
基金
英国惠康基金;
关键词
D O I
10.1038/nsmb1303
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1077 / 1083
页数:7
相关论文
共 47 条
[21]   Diagnosis of autosomal dominant retinitis pigmentosa by linkage-based exclusion screening with multiple locus-specific microsatellite markers. [J].
Kondo, H ;
Tahira, T ;
Mizota, A ;
Adachi-Usami, E ;
Oshima, K ;
Hayashi, K .
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2003, 44 (03) :1275-1281
[22]  
LESSER CF, 1993, GENETICS, V133, P851
[23]  
LIN RJ, 1985, J BIOL CHEM, V260, P4780
[24]  
Longtine MS, 1998, YEAST, V14, P953, DOI 10.1002/(SICI)1097-0061(199807)14:10<953::AID-YEA293>3.0.CO
[25]  
2-U
[26]   The human Prp8 protein is a component of both U2-and U12-dependent spliceosomes [J].
Luo, HBR ;
Moreau, GA ;
Levin, N ;
Moore, MJ .
RNA, 1999, 5 (07) :893-908
[27]   PAP-1, the mutated gene underlying the RP9 form of dominant retinitis pigmentosa, is a splicing factor [J].
Maita, H ;
Kitaura, H ;
Keen, TJ ;
Inglehearn, CF ;
Ariga, H ;
Iguchi-Ariga, SMM .
EXPERIMENTAL CELL RESEARCH, 2004, 300 (02) :283-296
[28]   Mutations in the pre-mRNA splicing-factor genes PRPF3, PRPF8, and PRPF31 in Spanish families with autosomal dominant retinitis pigmentosa [J].
Martínez-Gimeno, M ;
Gamundi, MJ ;
Hernan, I ;
Maseras, M ;
Millá, E ;
Ayuso, C ;
García-Sandoval, B ;
Beneyto, M ;
Vilela, C ;
Baiget, M ;
Antiñolo, G ;
Carballo, M .
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2003, 44 (05) :2171-2177
[29]   Mutations in the pre-mRNA splicing factor gene PRPC8 in autosomal dominant retinitis pigmentosa (RP13) [J].
McKie, AB ;
McHale, JC ;
Keen, TJ ;
Tarttelin, EE ;
Goliath, R ;
van Lith-Verhoeven, JJC ;
Greenberg, J ;
Ramesar, RS ;
Hoyng, CB ;
Cremers, FPM ;
Mackey, DA ;
Bhattacharya, SS ;
Bird, AC ;
Markham, AF ;
Inglehearn, CF .
HUMAN MOLECULAR GENETICS, 2001, 10 (15) :1555-1562
[30]   A role for Cajal bodies in the final steps of U2 snRNP biogenesis [J].
Nesic, D ;
Tanackovic, G ;
Krämer, A .
JOURNAL OF CELL SCIENCE, 2004, 117 (19) :4423-4433