Fridell R A, Benson R E, Hua J, Bogerd H P, Cullen B R
Department of Genetics, Duke University Medical Center, Durham, NC 27710, USA.
EMBO J. 1996 Oct 1;15(19):5408-14.
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 mis-localization 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).
脆性X综合征是由于缺乏脆性X智力低下蛋白（FMRP）的功能性形式的表达所致，FMRP是一种功能不明的细胞质RNA结合蛋白。在此，我们报告FMRP含有一个核输出信号（NES），该信号与最近在人类免疫缺陷病毒1型（HIV-1）的Rev调节蛋白中鉴定出的NES相似。这个FMRP NES的突变导致FMRP错误定位于细胞核。FMRP NES在FMR1基因的第14外显子内编码，从而解释了缺乏该外显子的FMRP天然异构体的异常核定位。FMRP的NES在介导依赖Rev的核RNA输出方面可以完全替代Rev NES，并特异性结合一种已被证明介导Rev NES功能的核孔蛋白样细胞辅因子。总之，这些发现表明FMRP的正常功能涉及进入细胞核，随后通过与HIV-1 Rev所利用的途径相同的途径输出。此外，这些数据增加了FMRP可能在介导其目前未定义的细胞RNA靶标的核输出中发挥作用的可能性。
