FXR1P相关microRNA的筛选与靶标鉴定及其在脆性X综合征发病中的分子机制研究

项目名称： FXR1P相关microRNA的筛选与靶标鉴定及其在脆性X综合征发病中的分子机制研究

项目编号： No.81200881

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 神经系统疾病、精神疾病

项目作者： 马云

作者单位： 南华大学

项目金额： 23万元

中文摘要： FXR1基因是脆性X综合征（FXS）重要的致病相关基因，但其具体致病机制仍不清楚。通过研读文献并结合课题组的前期研究，我们推测FXR1P可以同时结合miRNAs和mRNAs，FXR1P与miRNAs共同调控靶mRNAs的表达。本课题组前期研究表明：FXR1P是一种RNA结合蛋白，通过蛋白与RNA、蛋白与蛋白之间的相互作用影响神经、肌肉系统的正常发育。以申请者前期取得的研究成果为基础，课题组拟利用RNA结合蛋白免疫沉淀技术、Solexa 高通量测序和生物信息学手段分析，筛选FXR1P相关的miRNAs和mRNAs,并通过双荧光素酶报告基因系统鉴定候选miRNAs与mRNAs之间的靶标关系；同时运用实时荧光定量PCR技术深入研究FXR1P调控侯选miRNAs表达变化的机制。本项目对FXR1P-miRNA相互作用机制的研究，有望为阐明FXS的发病机制提供新的思路。

中文关键词： 脆性X相关蛋白1；微小RNA；靶mRNA；表达调控；

英文摘要： FXR1 is the crucial related gene of fragile X syndrom（FXS）, the specific pathogenic mechanism of which remains not clear. As reading some related references and the previous study of our group, the hypothesis that FXR1P is an RNA-binding protein that binds to miRNAs and mRNAs, then FXR1P and the interactive miRNA co-regulate the expression of mRNA was proposed.Our previous research indicates that FXR1P regulates the normal development of nervous and musclar system by the interaction between protein and RNA or protein and protein. Based on the previous research of applicant, by using the RNA-binding protein immunoprecipitation (RIP) technology, Solexa high throughput sequencing and bioinformatics assaying ,we plan to screen miRNAs and mRNAs binding to FXR1P; then luciferase report gene system will be used to identify the targeted relationship between the significant miRNA and mRNA; meanwhile, we can use Quantitative Real-Time PCR to further reasearch the mechanism of the changed expression of miRNA, which was regulated by FXR1P. This study of the mechanism of FXR1P-miRNA interaction is expected to help to elucidate the pathogenesis of FXS provides a new thinking.

英文关键词： FXR1P；miRNA；target mRA；expression regulation；