Translational Regulation of Fragile X Syndrome Gene

脆性 X 综合征基因的翻译调控

基本信息

批准号：
6550516
负责人：
JAE H LIM
金额：
$ 3.91万
依托单位：
BROWN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-07-01 至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/6550516
关键词：
RNA binding protein Xenopus oocyte cAMP response element binding protein dark adaptation fragile X syndromes genetic transcription genetic translation genetically modified animals green fluorescent proteins laboratory mouse laboratory rat messenger RNA nucleic acid repetitive sequence polyadenylate predoctoral investigator

项目摘要

DESCRIPTION (provided by applicant): Fragile X mental retardation syndrome is the most common form of inherited mental retardation. It is transmitted as a X-linked dominant trait with reduced penetrance and is associated with a fragile site known as FRAXA (Fragile site, X chromosome, A site) at Xq27.3. The pathogenesis of fragile X syndrome is thought to be due to a massive trinucleotide repeat expansion in the 5'UTR of the fragile X mental retardation-i gene (FMR1), which results in the loss of its protein product, FMRP. Although the precise function of FMRP has not yet been elucidated, it is believed to be a RNA-binding protein that associates with polyribosomes and the rough endoplasmic reticulum. And because FMRP is translated in the synapse in response to synaptic activation, it has been suggested to play important roles in protein translation and in synaptic plasticity. Interestingly, a growing body of evidence indicates a defect in translational processing of FMR1 as a potential mechanism leading to fragile X syndrome. Presently, however, the mechanism behind the regulation of FMR1 translation is poorly understood. Such understanding is necessary for elucidating the pathogenesis of fragile X syndrome and for identifying potential molecular targets for therapy. Therefore, I will examine the molecular basis behind the regulation and activation of FMR1 translation.

描述（由申请人提供）：脆性 X 型智力低下综合征是遗传性智力低下最常见的形式。它作为外显率降低的 X 连锁显性性状传播，并与 Xq27.3 处称为 FRAXA（脆弱位点，X 染色体，A 位点）的脆弱位点相关。脆性 X 综合征的发病机制被认为是由于脆性 X 智力低下基因 (FMR1) 5'UTR 中的大量三核苷酸重复扩增导致其蛋白质产物 FMRP 的丢失。尽管FMRP的精确功能尚未阐明，但据信它是一种RNA结合蛋白，与多核糖体和粗面内质网结合。由于 FMRP 在突触激活时被翻译，因此有人认为它在蛋白质翻译和突触可塑性中发挥着重要作用。有趣的是，越来越多的证据表明 FMR1 翻译加工缺陷是导致脆性 X 综合征的潜在机制。然而目前，人们对 FMR1 翻译调节背后的机制知之甚少。这种理解对于阐明脆性 X 综合征的发病机制和确定潜在的治疗分子靶点是必要的。因此，我将研究 FMR1 翻译调节和激活背后的分子基础。