THE DEVELOPMENTALLY-REGULATED DROSOPHILA GENE ROX8 ENCODES AN RRM-TYPE RNA-BINDING PROTEIN STRUCTURALLY RELATED TO HUMAN TIA-1-TYPE NUCLEOLYSINS

THE DEVELOPMENTALLY-REGULATED DROSOPHILA GENE ROX8 ENCODES AN RRM-TYPE RNA-BINDING PROTEIN STRUCTURALLY RELATED TO HUMAN TIA-1-TYPE NUCLEOLYSINS
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DOI:
10.1093/nar/21.16.3699
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发表时间:
1993-08-11
影响因子:
14.9
通讯作者:
BOURBON, HM
BOURBON, HM
中科院分区:
生物学2区
文献类型:
--
作者:
BRAND, S;BOURBON, HM

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我们报道了对一个新的黑腹果蝇基因rox8的分子分析,该基因是在基于聚合酶链反应(PCR)的筛选编码RRM型RNA结合多肽的序列过程中分离出来的。据预测,rox8基因编码一个50千道尔顿的蛋白质,它与最近描述的两种人类TIA - 1型核溶素在氨基酸序列上有广泛的相似性(总体一致性为46%;相似性为57% - 60%)。这些与细胞溶解颗粒相关的蛋白质在体外能结合多聚腺苷酸化序列,并在透化的靶细胞中引发DNA断裂,被怀疑参与由T淋巴细胞和自然杀伤细胞诱导的细胞凋亡途径。这三种蛋白质的结构相关性包括在N末端的三个串联重复的共有RNA识别基序以及在C末端的一个假定的膜靶向信号。从细胞学角度来看,rox8定位在第三染色体右臂的95D5 - 9区域。长度分别为3kb和3.3kb的两种rox8转录本是由于不同的多聚腺苷酸化位点在发育过程中受到调控的选择性使用而产生的,并且在果蝇的整个生命周期中积累情况不同。对rox8的分子特性描述是对一种与TIA - 1相关的蛋白质在果蝇RNA代谢和/或程序性细胞死亡中潜在作用进行遗传分析的第一步。
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 out 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.