Jin P, Warren S T
Howard Hughes Medical Institute and Departments of Biochemistry, Pediatrics and Genetics, Emory University School of Medicine, Rollins Research Center, Atlanta, GA 30322, USA.
Hum Mol Genet. 2000 Apr 12;9(6):901-8. doi: 10.1093/hmg/9.6.901.
Fragile X syndrome, a common form of inherited mental retardation, is mainly caused by massive expansion of CGG triplet repeats located in the 5'-untranslated region of the fragile X mental retardation-1 ( FMR1 ) gene. In patients with fragile X syndrome, the expanded CGG triplet repeats are hypermethylated and the expression of the FMR1 gene is repressed, which leads to the absence of FMR1 protein (FMRP) and subsequent mental retardation. FMRP is an RNA-binding protein that shuttles between the nucleus and cytoplasm. This protein has been implicated in protein translation as it is found associated with polyribosomes and the rough endoplasmic reticulum. We discuss here the recent progress made towards understanding the molecular mechanism of CGG repeat expansion and physiological function(s) of FMRP. These studies will not only help to illuminate the molecular basis of the general class of human diseases with trinucleotide repeat expansion but also provide an avenue to understand aspects of human cognition and intelligence.
脆性X综合征是遗传性智力迟钝的一种常见形式，主要由脆性X智力迟钝1（FMR1）基因5'非翻译区的CGG三联体重复序列大量扩增引起。在脆性X综合征患者中，扩增的CGG三联体重复序列发生高度甲基化，FMR1基因的表达受到抑制，导致FMR1蛋白（FMRP）缺失，进而引起智力迟钝。FMRP是一种在细胞核和细胞质之间穿梭的RNA结合蛋白。该蛋白与多核糖体和糙面内质网相关，因而参与蛋白质翻译过程。我们在此讨论了在理解CGG重复序列扩增的分子机制以及FMRP的生理功能方面所取得的最新进展。这些研究不仅有助于阐明由三核苷酸重复序列扩增引起的人类疾病的分子基础，还为理解人类认知和智力方面提供了途径。
