A Drosophila fragile X protein interacts with components of RNAi and ribosomal proteins
A Drosophila fragile X protein interacts with components of RNAi and ribosomal proteins
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DOI：
10.1101/gad.1022002
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发表时间：
2002-10-01
影响因子：
10.5
通讯作者：
Siomi, H
中科院分区：
文献类型：
--
作者：
Ishizuka, A;Siomi, MC;Siomi, H
脆性X综合征是一种常见的遗传性精神发育迟滞，由FMR 1表达缺失引起。FMR 1基因编码一种RNA结合蛋白，与翻译核糖体相关，并作为负翻译调节因子。在果蝇中，FMR 1蛋白的果蝇同源物（dFMR 1）结合并抑制微管相关蛋白Futsch的mRNA编码的翻译。我们已经分离出dFMR1相关复合物，它包括两种核糖体蛋白L5和L11，沿着还有5S RNA. dFMR 1复合物还含有Argonaute2（AG02）和果蝇p68 RNA解旋酶（Dmp 68）的同源物。AGO 2是RNA诱导沉默复合物（RISC）的重要组成部分，RISC是一种介导果蝇RNA干扰（RNAi）的序列特异性核酸酶复合物。我们进一步表明，dFMR 1与Dicer（RNAi途径的另一个重要组成部分）和体内microRNA（miRNA）相关，表明dFMR 1是RNAi相关装置的一部分。我们的研究结果提出了一个模型，其中RNAi和dFMR1介导的翻译控制途径在果蝇相交。我们的研究结果还提出了RNAi相关机制缺陷可能导致人类疾病的可能性。
Fragile X syndrome is a common form of inherited mental retardation caused by the loss of FMR1 expression. The FMR1 gene encodes an RNA-binding protein that associates with translating ribosomes and acts as a negative translational regulator. In Drosophila, the fly homolog of the FMR1 protein (dFMR1) binds to and represses the translation of an mRNA encoding of the microtuble-associated protein Futsch. We have isolated a dFMRl -associated complex that includes two ribosomal proteins, L5 and L11, along with 5S RNA. The dFMR1 complex also contains Argonaute2 (AG02) and a Drosophila homolog of p68 RNA helicase (Dmp68). AGO2 is an essential component for the RNA-induced silencing complex (RISC), a sequence-specific nuclease complex that mediates RNA interference (RNAi) in Drosophila. We show that Dmp68 is also required for efficient RNAL We further show that dFMR1 is associated with Dicer, another essential component of the RNAi pathway, and microRNAs (miRNAs) in vivo, suggesting that dFMR1 is part of the RNAi-related apparatus. Our findings suggest a model in which the RNAi and dFMR1-mediated translational control pathways intersect in Drosophila. Our findings also raise the possibility that defects in an RNAi-related machinery may cause human disease.