Boon Kum-Loong, Grainger Richard J, Ehsani Parastoo, Barrass J David, Auchynnikava Tatsiana, Inglehearn Chris F, Beggs Jean D
Wellcome Trust Centre for Cell Biology, University of Edinburgh, King's Buildings, Mayfield Road, Edinburgh EH9 3JR, UK.
Nat Struct Mol Biol. 2007 Nov;14(11):1077-83. doi: 10.1038/nsmb1303. Epub 2007 Oct 14.
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.
Prp8蛋白（Prp8p）是一种高度保守的前体mRNA剪接因子，也是剪接体U5小核核糖核蛋白（snRNP）的一个组成部分。尽管它在全身广泛表达，但人类Prp8p C末端的突变会导致视网膜特异性疾病色素性视网膜炎（RP）。U5 snRNP的生物发生过程目前了解甚少。我们提供了酵母中一种细胞质前体U5 snRNP的证据，该前体缺乏成熟的U5 snRNP成分Brr2p，并且其有效核输入依赖于Prp8p中的核定位信号。Brr2p与U5 snRNP的结合发生在细胞核内。酵母中Prp8p的RP突变导致前体U5 snRNP在细胞核中积累，这显然是由于破坏了Prp8p与Brr2p之间的相互作用所致。因此，我们提出了一种新的U5 snRNP复合物组装途径，该途径会被导致人类RP的突变所破坏。
