Brand S, Bourbon H M
Centre de Biologie du Développement, UMR 9925 CNRS/UPS, Université Paul Sabatier, Toulouse, France.
Nucleic Acids Res. 1993 Aug 11;21(16):3699-704. doi: 10.1093/nar/21.16.3699.
We report the molecular analysis of a novel Drosophila melanogaster gene, rox8, isolated in a PCR-based screen for sequences encoding RRM-type RNA-binding polypeptides. The rox8 gene is predicted to encode a 50-kilodalton protein displaying extensive amino acid sequence similarities (46% overall identity; 57 to 60% similarity) to the two recently described human TIA-1-type nucleolysins. These cytolytic granule associated proteins, which bind polyadenylated sequences in vitro and trigger DNA fragmentation in permeabilized target cells, are suspected to participate in the apoptotic cell death pathway induced by T-lymphocytes and natural killer cells. The structural relatedness of the three proteins includes three tandemly-repeated consensus RNA-recognition motifs at the N-terminal end and a putative membrane targeting signal at the C-terminal end. rox8 cytologically maps to 95D5-9 on the right arm of the third chromosome. Two rox8 transcripts of 3 and 3.3 kb in length, respectively, result from a developmentally-modulated alternative usage of different polyadenylation sites and are differentially accumulated throughout the fly life cycle. Molecular characterization of rox8 represents the first step in a genetic analysis of the potential roles of a TIA-1-related protein in RNA metabolism and/or programmed cell death in Drosophila.
我们报告了对一个新的果蝇基因rox8的分子分析,该基因是在基于PCR的筛选中分离得到的,用于筛选编码RRM型RNA结合多肽的序列。rox8基因预计编码一种50千道尔顿的蛋白质,与最近描述的两种人类TIA-1型核溶解素显示出广泛的氨基酸序列相似性(总体同一性为46%;相似性为57%至60%)。这些与溶细胞颗粒相关的蛋白质,在体外结合多聚腺苷酸化序列并在通透的靶细胞中引发DNA片段化,被怀疑参与由T淋巴细胞和自然杀伤细胞诱导的凋亡细胞死亡途径。这三种蛋白质的结构相关性包括在N末端有三个串联重复的共有RNA识别基序,在C末端有一个假定的膜靶向信号。rox8在细胞学上定位于第三条染色体右臂的95D5-9。分别长度为3和3.3 kb的两种rox8转录本,是由不同聚腺苷酸化位点的发育调节性交替使用产生的,并且在果蝇的整个生命周期中差异积累。rox8的分子特征代表了对TIA-1相关蛋白在果蝇RNA代谢和/或程序性细胞死亡中的潜在作用进行遗传分析的第一步。