The fragile X mental retardation protein is a ribonucleoprotein containing both nuclear localization and nuclear export signals
The fragile X mental retardation protein is a ribonucleoprotein containing both nuclear localization and nuclear export signals
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DOI：
10.1093/hmg/5.8.1083
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发表时间：
1996-08-01
影响因子：
3.5
通讯作者：
Warren, ST
中科院分区：
文献类型：
--
作者：
Eberhart, DE;Malter, HE;Warren, ST
脆性X综合征是由FMR1基因编码的蛋白质FMRP缺失引起的一种常见的智力低下原因，FMRP是一种与核糖体相关的未知功能的RNA结合蛋白，为了深入了解FMRP的功能，我们对FMRP截断和融合结构进行了免疫定位分析，发现FMRP的氨基端有一个核定位信号(NLS)，以及由外显子14编码的核输出信号(NES)，包含FMRP NES的17个氨基酸多肽与最近为HIV-1 Rev和PKI描述的NES基序非常相似，足以直接核输出微量注射蛋白。蔗糖梯度分析表明，FMRP核糖体结合是RNA依赖的，EDTA处理后的核糖核蛋白(RNP)中存在FMRP。这些数据与新生的FMRP进入细胞核组装成mRNP颗粒，然后输出回细胞质是一致的，表明脆性X综合征可能是由于通常与FMRP结合的转录本的翻译改变造成的。
Fragile X syndrome is a frequent cause of mental retardation resulting from the absence of FMRP, the protein encoded by the FMR1 gene, FMRP is an RNA-binding protein of unknown function which is associated with ribosomes, To gain insight into FMRP function, we performed immunolocalization analysis of FMRP truncation and fusion constructs which revealed a nuclear localization signal (NLS) in the amino terminus of FMRP as well as a nuclear export signal (NES) encoded by exon 14, A 17 amino acid peptide containing the FMRP NES, which closely resembles the NES motifs recently described for HIV-1 Rev and PKI, is sufficient to direct nuclear export of a microinjected protein conjugate, Sucrose gradient analysis shows that FMRP ribosome association is RNA-dependent and FMRP is found in ribonucleoprotein (RNP) particles following EDTA treatment. These data are consistent with nascent FMRP entering the nucleus to assemble into mRNP particles prior to export back into the cytoplasm and suggests that fragile X syndrome may result from altered translation of transcripts which normally bind to FMRP.