C9orf72 六核酸重复RNA驱动通过全基因组DNA:RNA混合G-四重复的转录失调
Honghe Liu1, Mingming Liu1, Yang Liu1
1Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Neuroscience, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
Neuron
|February 5, 2026
概括
在C9orf72中,GGGGCC重复RNA扩张通过形成DNA:RNA杂交G-四复合体,导致神经退行性疾病. 这种结构破坏了基因调节,导致神经元脆弱性和疾病.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 遗传学 是一个
- 分子生物学分子生物学
背景情况:
- C9orf72 六核酸重复扩张是肌缩性侧面硬化症和前性痴呆症的主要遗传原因.
- 通过重复RNAs促进神经退行的精确机制尚未完全理解.
研究的目的:
- 研究GGGGCC重复RNA如何与基因组相互作用并影响患者细胞中的基因表达.
- 阐明RNA介导的转录干扰的结构基础.
主要方法:
- 对GGGGCC重复RNA的全基因组染色体参与分析.
- 生物化学分析,单分子成像和本地双硫酸盐测序.
- 在患者衍生模型中评估神经元脆弱性和基因失调.
主要成果:
- GGGGCC重复RNA在全基因组内结合,特别是在促进子区域,阻碍RNA聚合酶II和转录因子.
- 重复RNA形成内在DNA:RNA与DNA混合的G-四重复合体 (HQs),导致转录干扰.
- 稳定HQs增加神经元对压力的脆弱性,而纠正基因失调会增强抵抗力.
结论:
- GGGGCC重复RNA形成了致病性DNA:RNA杂交G-四重复,破坏了基因调节.
- 这种机制有助于C9orf72相关疾病的神经退行.
- 针对这些结构或恢复基因表达可能提供治疗策略.
相关概念视频
Genome-wide Association Studies-GWAS
15.7K
Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
GWAS does not require the identification of the target gene involved in...
15.7K
Viruses with RNA Genomes
935
RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
935
Transcription Elongation Factors
14.0K
Transcription elongation is a dynamic process that alters depending upon the sequence heterogeneity of the DNA being transcribed. Hence, it is not surprising that the elongation complex's composition also varies along the way while transcribing a gene.
The transcription elongation is regulated via pausing of RNA polymerase on several occasions during transcription. In bacteria, these halts are necessary because the transcription of DNA into mRNA is coupled to the translation of that mRNA...
The transcription elongation is regulated via pausing of RNA polymerase on several occasions during transcription. In bacteria, these halts are necessary because the transcription of DNA into mRNA is coupled to the translation of that mRNA...
14.0K
Transcription Factors
82.8K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
82.8K
Transcription
156.8K
Overview
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds...
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds...
156.8K
Prokaryotic Transcriptional Activators and Repressors
25.5K
The organization of prokaryotic genes in their genome is notably different from that of eukaryotes. Prokaryotic genes are organized, such that the genes for proteins involved in the same biochemical process or function are located together in groups. This group of genes, along with their regulatory elements, are collectively known as an operon. The functional genes in an operon are transcribed together to give a single strand of mRNA known as polycistronic mRNA.
Transcription of prokaryotic...
Transcription of prokaryotic...
25.5K


