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由C9ORF72六核苷酸扩增突变转录的核内（G4C2）n RNA病灶形成副斑点样结构Intranuclear (G4C2)n RNA foci, transcribed from C9ORF72 hexanucleotide expansion mutation, form paraspeckle-like structures |
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| 课程网址: | http://videolectures.net/encals2017_bajc_cesnik_expansion_mutatio... |
| 主讲教师: | Ana Bajc Česnik |
| 开课单位: | 约瑟夫·斯特凡研究所 |
| 开课时间: | 2017-07-21 |
| 课程语种: | 英语 |
| 中文简介: |  |
| 课程简介: | Expansion of GGGGCC hexanucleotide repeat in the C9ORF72 gene is the most common pathogenic mutation in the families with autosomal dominant frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS) and FTD/ALS. The expanded repeat is transcribed from the sense and the antisense strand and forms intranuclear RNA foci. Here we show that the core paraspeckle proteins SFPQ, NONO and PSPC1 bind to (G4C2)n RNA in vitro, co-localise with intranuclear RNA foci in cells transfected with the expanded repeats and to a lesser extent in post-mortem brain tissue. Paraspeckles are nuclear structures functioning in nuclear retention of adenosine to inosine edited RNA. They form on a backbone of the long non-coding RNA NEAT1. We demonstrated that the presence of RNA foci increased the number of SFPQ stained subnuclear bodies, however only a small fraction of (G4C2)n RNA foci co-localised with NEAT1. Sense RNA foci lead to nuclear remodelling, as shown by an increased number of SFPQ-stained subnuclear bodies, which form independently of the known paraspeckle platform NEAT1. Thus, our results suggest that (G4C2)n RNA may lead to formation of paraspeckle-like structures, which may compete with NEAT1 for associated proteins and modulate nuclear compartmentalization of paraspeckle- bound RNAs. |
| 关 键 词: | RNA病灶; 副斑点; 核结构 |
| 课程来源: | 视频讲座网 |
| 数据采集: | 2021-12-17：zkj |
| 最后编审: | 2021-12-17：zkj |
| 阅读次数: | 90 |