Different targets for the fragile X-related proteins revealed by their distinct nuclear localizations.
Different targets for the fragile X-related proteins revealed by their distinct nuclear localizations.
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DOI：
10.1093/hmg/8.5.863
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发表时间：
1999-05
影响因子：
3.5
通讯作者：
Filippo Tamanini;Carola Bontekoe;C. Bakker;L. Unen;Burcu Anar;Rob Willemsen;Minoru Yoshida;Hans Galjaard;B. Oostra;A. Hoogeveen
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文献类型：
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作者：
Filippo Tamanini;Carola Bontekoe;C. Bakker;L. Unen;Burcu Anar;Rob Willemsen;Minoru Yoshida;Hans Galjaard;B. Oostra;A. Hoogeveen
脆性X综合征是由于缺乏脆性X智力低下蛋白（FMRP）引起的。FMRP及其结构同源物FXR1P和FXR2P形成RNA结合蛋白（FXR蛋白）家族。这三种蛋白质与多聚核糖体结合为细胞质mRNP颗粒。在这里，我们发现少量的FMRP，FXR1P和FXR2P穿梭于细胞质和细胞核之间。一个严重影响脆性X患者（FMRPI304 N）的突变FMRP不与多聚核糖体和穿梭更频繁地比正常FMRP，表明与多聚核糖体的协会调节穿梭过程。使用来普霉素B，我们证明，运输的FXR蛋白质的细胞核是介导的出口受体exportin1。最后，两种FXR蛋白核输出信号的失活表明，FMRP穿梭于细胞质和核质之间，而FXR2P穿梭于细胞质和核仁之间。因此，对FXR蛋白质使用的穿梭路线的分子解剖表明它们转运不同的RNA。
Fragile X syndrome is caused by the absence of the fragile X mental retardation protein (FMRP). FMRP and its structural homologues FXR1P and FXR2P form a family of RNA-binding proteins (FXR proteins). The three proteins associate with polyribosomes as cytoplasmic mRNP particles. Here we show that small amounts of FMRP, FXR1P and FXR2P shuttle between cytoplasm and nucleus. Mutant FMRP of a severely affected fragile X patient (FMRPI304N) does not associate with polyribosomes and shuttles more frequently than normal FMRP, indicating that the association with polyribosomes regulates the shuttling process. Using leptomycin B we demonstrate that transport of the FXR proteins out of the nucleus is mediated by the export receptor exportin1. Finally, inactivation of the nuclear export signal in two FXR proteins shows that FMRP shuttles between cytoplasm and nucleoplasm, while FXR2P shuttles between cytoplasm and nucleolus. Therefore, molecular dissection of the shuttling routes used by the FXR proteins suggests that they transport different RNAs.