Ashley C T, Wilkinson K D, Reines D, Warren S T
Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322.
Science. 1993 Oct 22;262(5133):563-6. doi: 10.1126/science.7692601.
Fragile X syndrome is the result of transcriptional suppression of the gene FMR1 as a result of a trinucleotide repeat expansion mutation. The normal function of the FMR1 protein (FMRP) and the mechanism by which its absence leads to mental retardation are unknown. Ribonucleoprotein particle (RNP) domains were identified within FMRP, and RNA was shown to bind in stoichiometric ratios, which suggests that there are two RNA binding sites per FMRP molecule. FMRP was able to bind to its own message with high affinity (dissociation constant = 5.7 nM) and interacted with approximately 4 percent of human fetal brain messages. The absence of the normal interaction of FMRP with a subset of RNA molecules might result in the pleiotropic phenotype associated with fragile X syndrome.
脆性X综合征是由于三核苷酸重复扩增突变导致基因FMR1转录抑制的结果。FMR1蛋白（FMRP）的正常功能及其缺失导致智力迟钝的机制尚不清楚。在FMRP中鉴定出核糖核蛋白颗粒（RNP）结构域，并且显示RNA以化学计量比结合，这表明每个FMRP分子有两个RNA结合位点。FMRP能够以高亲和力结合其自身的信使RNA（解离常数=5.7 nM），并与大约4%的人类胎儿脑信使RNA相互作用。FMRP与一部分RNA分子的正常相互作用缺失可能导致与脆性X综合征相关的多效性表型。
