Inoue S B, Siomi M C, Siomi H
Institute for Genome Research, University of Tokushima, Japan.
J Med Invest. 2000 Aug;47(3-4):101-7.
Fragile X syndrome is the most common form of inherited mental retardation Mutations which abolish expression of an X-linked gene, FMR1, result in pathogenesis of the disease. FMR1 encodes a cytoplasmic RNA-binding protein which interacts with two autosomal homologs, FXR1 and FXR2. These proteins are highly expressed in neurons. In addition, the FMR1/FXR proteins are associated with ribosomes. Given their RNA-binding activity and association with ribosomes, these proteins are hypothesized to bind to specific RNAs and regulate their expression at translational levels in a manner critical for correct development of neurons. Much progress has been made in FMR1 research over the past several years, but little light has yet to be shed on the physiological function of these proteins. It will be critical to define the biochemical properties of these proteins, and identify potential downstream targets to clarify the molecular mechanisms underlying the potential roles of these proteins in translation. A basic understanding of the function of this new family of RNA-binding proteins should then allow us to begin to address the question of how the lack of FMR1 expression leads to symptoms in fragile X syndrome.
脆性X综合征是遗传性智力迟钝最常见的形式。导致X连锁基因FMR1表达缺失的突变会引发该疾病的发病机制。FMR1编码一种细胞质RNA结合蛋白，该蛋白与两个常染色体同源物FXR1和FXR2相互作用。这些蛋白质在神经元中高度表达。此外，FMR1/FXR蛋白与核糖体相关联。鉴于它们的RNA结合活性以及与核糖体的关联，推测这些蛋白质可结合特定的RNA，并以对神经元正常发育至关重要的方式在翻译水平上调节其表达。在过去几年中，FMR1研究取得了很大进展，但这些蛋白质的生理功能仍不清楚。明确这些蛋白质的生化特性并确定潜在的下游靶点，以阐明这些蛋白质在翻译中潜在作用的分子机制至关重要。对这个新的RNA结合蛋白家族功能的基本了解，将使我们能够开始解决FMR1表达缺失如何导致脆性X综合征症状的问题。
