A nuclear role for the fragile X mental retardation protein
A nuclear role for the fragile X mental retardation protein
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DOI：
10.1002/j.1460-2075.1996.tb00924.x
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发表时间：
1996-10-01
期刊：
影响因子：
11.4
通讯作者：
Cullen, BR
中科院分区：
文献类型：
--
作者：
Fridell, RA;Benson, RE;Cullen, BR
脆性X综合征是由于脆性X智力低下蛋白（FMRP）的功能形式表达缺乏所致，FMRP是一种功能不确定的细胞质RNA结合蛋白。在此，我们报告FMRP含有一个核输出信号（内斯），该信号与最近在人类免疫缺陷病毒1型（HIV-1）Rev调节蛋白中发现的内斯相似。该FMRP内斯的突变导致FMRP错误定位于细胞核。FMRP内斯在FMR 1基因的外显子14内编码，从而解释了缺乏该外显子的FMRP天然同种型的异常核定位，FMRP的内斯可以完全取代Rev内斯介导Rev依赖的核RNA输出，并特异性结合核孔蛋白-与已显示介导Rev内斯功能的细胞辅因子一样，这些发现一起证明FMRP的正常功能包括进入细胞核，然后通过与HIV-1 Rev所利用的途径相同的途径输出。此外，这些数据提高了FMRP可能在介导其目前未确定的细胞RNA靶的核输出中起作用的可能性。
Fragile X syndrome results from lack of expression of a functional form of Fragile X mental retardation protein (FMRP), a cytoplasmic RNA-binding protein of uncertain function, Here, we report that FMRP contains a nuclear export signal (NES) that is similar to the NES recently identified in the Rev regulatory protein of human immunodeficiency virus type 1 (HIV-1). Mutation of this FMRP NES results in mislocalization of FMRP to the cell nucleus, The FMRP NES is encoded within exon 14 of the FMR1 gene, thus explaining the aberrant nuclear localization of a natural isoform of FMRP that lacks this exon, The NES of FMRP can substitute fully for the Rev NES in mediating Rev-dependent nuclear RNA export and specifically binds a nucleoporin-like cellular cofactor that has been shown to mediate Rev NES function, Together, these findings demonstrate that the normal function of FMRP involves entry into the nucleus followed by export via a pathway that is identical to the one utilized by HIV-1 Rev, In addition, these data raise the possibility that FMRP could play a role in mediating the nuclear export of its currently undefined cellular RNA target(s).