通过ATAC-seq和ChIP实验发现,(GGGGCC)n的异常扩增导致C9orf72启动子区的染色体结构和表观遗传修饰异常。进一步研究证实,敲降DAXX,能过纠正(GGGGCC)n扩增突变导致的染色体异常,从而上调正常条件下和应激条件下的 C9orf72转录表达。更重要...
研究发现,CRISPR-Cas13d可以被优化以特异性地靶向C9orf72-ALS病人细胞中的GGGGCC重复RNA,并显著减少源自GGGGCC重复RNA的多聚二肽重复蛋白的翻译。 在这项研究中,研究人员首先构建了绿色荧光蛋白报告系统并比较了Cas13b和Cas13d靶向GGGGCC...
1Purα修复GGGGCC六核苷酸重复扩增非编码RNA介导的神经细胞毒性硕士研究生:张瑜导师:**莲副教授华中科技大学同济医学院解剖学系组织胚胎学室武汉430030摘要肌萎缩性脊髓侧索硬化症(Amyotrophiclateralsclerosis,ALS)和额颞叶痴呆(Frontotemporaldementia,FTD)都是神经退行性疾病,均呈渐进性发展最终导致瘫痪或死亡,在临床表现、...
Mutant r(GGGGCC)n-containing transcripts aggregate in nuclear foci possibly sequestering repeat-binding proteins, suggesting a toxic RNA pathogenesis. We demonstrate that the r(GGGGCC)n RNA but not the C-rich r(GGCCCC)n RNA forms extremely stable uni- and multimolecular parallel G-quadruplex ...
RNA of the expanded repeat (r(GGGGCC)exp) forms nuclear foci or undergoes repeat-associated non-ATG (RAN) translation, producing “c9RAN proteins.” Since neutralizing r(GGGGCC)exp could inhibit these potentially toxic events, we sought to identify small-molecule binders of r(GGGGCC)exp. ...
An expanded GGGGCC hexanucleotide of more than 30 repeats (termed (G4C2)30+) within C9orf72 is the most prominent mutation in familial frontotemporal degeneration (FTD) and amyotrophic lateral sclerosis (ALS) (termed C9+). Through an unbiased large-scale screen of (G4C2)49-expressing Drosop...
摘要: 目的 检测中国内地家族性肌萎缩侧索硬化(fALS)患者9号染色体开放阅读框72(C9ORF72)基因六核苷酸(GGGGCC)中度重复扩增(重复数为20 ～ 30)的发生率,分析其临床表型并探讨C9ORF72基因中度重复对中国内地fALS患者的意义.方法 对2007-2013年就诊于北京大学第三医院的62例fALS患者进行临床资料收集并提取DNA,检测C9...
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Genetic analysis revealed the hexanucleotide repeat expansion GGGGCC within the regulatory region of the gene C9orf72 as the most common cause of familial amyotrophic lateral sclerosis and the second most common cause of frontotemporal lobar degeneration. Since repeat expansions might cause RNA toxicity ...
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