Tamanini F, Bontekoe C, Bakker C E, van Unen L, Anar B, Willemsen R, Yoshida M, Galjaard H, Oostra B A, Hoogeveen A T
Department of Clinical Genetics and Center for Biomedical Genetics, Erasmus University, PO Box 1738, 3000 DR Rotterdam, The Netherlands.
Hum Mol Genet. 1999 May;8(5):863-9. doi: 10.1093/hmg/8.5.863.
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.
脆性X综合征由脆性X智力低下蛋白（FMRP）缺失引起。FMRP及其结构同源物FXR1P和FXR2P构成了一个RNA结合蛋白家族（FXR蛋白）。这三种蛋白作为细胞质mRNA颗粒与多核糖体结合。在此我们表明，少量的FMRP、FXR1P和FXR2P在细胞质和细胞核之间穿梭。一名脆性X严重患者的突变型FMRP（FMRPI304N）不与多核糖体结合，且比正常FMRP更频繁地穿梭，这表明与多核糖体的结合调节了穿梭过程。使用放线菌素B，我们证明FXR蛋白从细胞核输出是由输出受体exportin1介导的。最后，对两种FXR蛋白中核输出信号的失活表明，FMRP在细胞质和核质之间穿梭，而FXR2P在细胞质和核仁之间穿梭。因此，对FXR蛋白所使用的穿梭途径的分子剖析表明它们运输不同的RNA。
