Department of Neurology, Northwestern University Feinberg Medical School, Chicago, IL 60611, USA.
Protein Cell. 2010 Mar;1(3):267-74. doi: 10.1007/s13238-010-0035-9. Epub 2010 Apr 17.
Retinitis pigmentosa is a leading cause of blindness and a progressive retinal disorder, affecting millions of people worldwide. This disease is characterized by photoreceptor degeneration, eventually leading to complete blindness. Autosomal dominant (adRP) has been associated with mutations in at least four ubiquitously expressed genes encoding pre-mRNA splicing factors-Prp3, Prp8, Prp31 and PAP1. Biological function of adRP-associated splicing factor genes and molecular mechanisms by which mutations in these genes cause cell-type specific photoreceptor degeneration in humans remain to be elucidated. To investigate the in vivo function of these adRP-associated splicing factor genes, we examined Drosophila in which expression of fly Prp31 homolog was down-regulated. Sequence analyses show that CG6876 is the likely candidate of Drosophila melanogaster Prp31 homolog (DmPrp31). Predicted peptide sequence for CG6876 shows 57% similarity to the Homo sapiens Prp31 protein (HsPrp31). Reduction of the endogenous Prp31 by RNAi-mediated knockdown specifically in the eye leads to reduction of eye size or complete absence of eyes with remarkable features of photoreceptor degeneration and recapitulates the bimodal expressivity of human Prp31 mutations in adRP patients. Such transgenic DmPrp31RNAi flies provide a useful tool for identifying genetic modifiers or interacting genes for Prp31. Expression of the human Prp31 in these animals leads to a partial rescue of the eye phenotype. Our results indicate that the Drosophila CG6876 is the fly ortholog of mammalian Prp31 gene.
色素性视网膜炎是一种主要的致盲原因，也是一种进行性视网膜疾病，影响着全球数百万人。这种疾病的特征是光感受器退化，最终导致完全失明。常染色体显性遗传（adRP）与至少四个普遍表达的编码前体 mRNA 剪接因子的基因中的突变有关-Prp3、Prp8、Prp31 和 PAP1。adRP 相关剪接因子基因的生物学功能以及这些基因中的突变如何导致人类特定细胞类型的光感受器退化的分子机制仍有待阐明。为了研究这些 adRP 相关剪接因子基因的体内功能，我们研究了果蝇，其中果蝇 Prp31 同源物的表达被下调。序列分析表明，CG6876 可能是果蝇 Prp31 同源物（DmPrp31）的候选基因。CG6876 的预测肽序列与人类 Prp31 蛋白（HsPrp31）有 57%的相似性。通过 RNAi 介导的敲低特异性地在眼睛中降低内源性 Prp31 的表达会导致眼睛大小减小或完全没有眼睛，具有光感受器退化的显著特征，并重现了 adRP 患者中人类 Prp31 突变的双峰表达性。这种转基因 DmPrp31RNAi 果蝇为鉴定 Prp31 的遗传修饰因子或相互作用基因提供了有用的工具。在这些动物中表达人类 Prp31 会导致眼部表型的部分挽救。我们的结果表明，果蝇 CG6876 是哺乳动物 Prp31 基因的果蝇同源物。
