Sci. Transl. Med:研究揭示自闭症发病机理
2012-04-10 刘纯 生物谷
4月4日,国际期刊《科学转化医学》(Science Translational Medicine)杂志发表了美国南加州大学的研究成果,研究者认为一段3.9kb的非编码RNA或导致了自闭症的发生。 自闭症又称孤独症,被归类为一种由于神经系统失调导致的发育障碍,其病征包括不正常的社交能力、沟通能力、兴趣和行为模式。自闭症患者有稀有突变和拷贝数的变异,但引起这一疾病的突变尚不清楚。 为找到导致自闭症
4月4日,国际期刊《科学转化医学》(Science Translational Medicine)杂志发表了美国南加州大学的研究成果,研究者认为一段3.9kb的非编码RNA或导致了自闭症的发生。
自闭症又称孤独症,被归类为一种由于神经系统失调导致的发育障碍,其病征包括不正常的社交能力、沟通能力、兴趣和行为模式。自闭症患者有稀有突变和拷贝数的变异,但引起这一疾病的突变尚不清楚。
为找到导致自闭症的基因和信号通路,研究者做了一项GWAS调查,结果表明,自闭症与SNP rs4307059显著相关,rs4307059位于基因贫乏的5p14.1染色体上,5p14.1可转录出一段3.9kb的非编码RNA。而这段非编码RNA正是由膜突蛋白假基因(moesin pseudogene 1,MSNP1)的反义链编码,因此研究人员将其称为MSNP1AS(moesin pseudogene 1,antisense)。
MSNP1AS与膜突蛋白的RNA可互补配对,而膜突蛋白的主要功能是调节神经元结构。自闭症患者的大脑皮层中MSNP1AS非编码RNA的表达量是正常人的12.7倍,而自闭症患者大脑中的膜突蛋白表达量没有明显改变,但在人细胞系中过量表达MSNP1AS时,膜突蛋白的表达量降低。
尽管自闭症患者大脑中的膜突蛋白表达量没有明显改变,但自闭症患者大脑皮层膜突蛋白表达量改变只发生在特定时期发育时期。(生物谷Bioon.com)
doi:10.1126/scitranslmed.3003479
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PMID:
A Noncoding RNA Antisense to Moesin at 5p14.1 in Autism
Tara Kerin, Anita Ramanathan, Kasey Rivas, Nicole Grepo, Gerhard A. Coetzee and Daniel B. Campbe
People with autism spectrum disorder (ASD) are characterized by deficits in social interaction, language, and behavioral flexibility. Rare mutations and copy number variations have been identified in individuals with ASD, but in most patients, the causal variants remain unknown. A genome-wide association study (GWAS), designed to identify genes and pathways that contribute to ASD, indicated a genome-wide significant association of ASD with the single-nucleotide polymorphism (SNP) rs4307059 (P = 10?10), which is located in a gene-poor region of chromosome 5p14.1. We describe here a 3.9-kb noncoding RNA that is transcribed from the region of the chromosome 5p14.1 ASD GWAS association SNP. The noncoding RNA was encoded by the opposite (antisense) strand of moesin pseudogene 1 (MSNP1), and we therefore designated it as MSNP1AS (moesin pseudogene 1, antisense). Chromosome 5p14.1 MSNP1AS was 94% identical and antisense to the X chromosome transcript of MSN, which encodes a protein (moesin) that regulates neuronal architecture. Individuals who carry the ASD-associated rs4307059 T allele showed increased expression of MSNP1AS. The MSNP1AS noncoding RNA bound to MSN, was highly overexpressed (12.7-fold) in postmortem cerebral cortex of individuals with ASD, and could regulate levels of moesin protein in human cell lines. These data reveal a biologically functional element that may contribute to ASD risk.
作者:刘纯
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