Siomi H, Siomi M C, Nussbaum R L, Dreyfuss G
Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia 19104-6148.
Cell. 1993 Jul 30;74(2):291-8. doi: 10.1016/0092-8674(93)90420-u.
Fragile X syndrome is one of the most common human genetic diseases and the most common cause of hereditary mental retardation. The gene that causes fragile X syndrome, FMR1, was recently identified and sequenced and found to encode a putative protein of unknown function. Here we report that FMR1 contains two types of sequence motifs recently found in RNA-binding proteins: an RGG box and two heterogeneous nuclear RNP K homology domains. We also demonstrate that FMR1 binds RNA in vitro. Using antibodies to FMR1, we detect its expression in divergent organisms and in cells of unaffected humans, but fragile X-affected patients express little or no FMR1. These findings demonstrate that FMR1 expression is directly correlated with the fragile X syndrome and suggest that anti-FMR1 antibodies will be important for diagnosis of fragile X syndrome. Furthermore, the RNA binding activity of FMR1 opens the way to understanding the function of FMR1.
脆性X综合征是最常见的人类遗传疾病之一，也是遗传性智力迟钝的最常见病因。导致脆性X综合征的基因FMR1最近已被鉴定和测序，并发现它编码一种功能未知的假定蛋白质。在此我们报告，FMR1含有最近在RNA结合蛋白中发现的两种序列基序：一个RGG框和两个不均一核RNP K同源结构域。我们还证明FMR1在体外能结合RNA。使用针对FMR1的抗体，我们在不同生物以及未受影响的人类细胞中检测到了它的表达，但脆性X综合征患者表达的FMR1很少或根本不表达。这些发现表明FMR1的表达与脆性X综合征直接相关，并提示抗FMR1抗体对脆性X综合征的诊断将具有重要意义。此外，FMR1的RNA结合活性为理解FMR1的功能开辟了道路。
