单分子成像揭示了C9ORF72-ALS/FTD中的扩展RNA重复的之间明显的延长和移动态
Malgorzata J Latallo1,2, Shaopeng Wang1,2,3,4, Daoyuan Dong3,4
1Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Nature communications
|September 11, 2023
概括
在C9ORF72相关的ALS/FTD中,有毒双重复 (DPR) 蛋白质的产生是通过翻译速度和移调节的. 与核糖体相关的质量控制因素也调节了DPR合成,提供治疗点.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
背景情况:
- C9ORF72重复扩张导致ALS和FTD.
- 有毒二重复 (DPR) 蛋白质与病变发生有关.
- 从重复RNA合成DPR的机制尚未完全理解.
研究的目的:
- 调查不同DPR的翻译动态.
- 阐明框架转移在DPR制作中的作用.
- 为了确定与核糖体相关的质量控制 (RQC) 因素的参与.
主要方法:
- 单分子成像技术用于测量翻译动态.
- 双色单分子转换试验可视化移.
- 测试以评估RQC因子的作用 (ZNF598,Pelota).
主要成果:
- 不同的DPR之间翻译延长率有很大差异 (GP比GA慢,GR最慢).
- 重复扩展增强了移,尽管总体频率较低.
- 从GR到GA的移动比从GA到GR更频繁.
- RQC因子ZNF598和Pelota调节了DPR的翻译动态.
- 重复RNA序列对于激活RQC途径至关重要.
结论:
- 多个翻译步骤,包括延长和移,控制DPR生产.
- 重复扩展影响翻译动态和RQC路径激活.
- 了解这些机制是开发C9ORF72-ALS/FTD治疗方法的关键.
相关概念视频
RNA Splicing
Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
Alternative RNA Splicing
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
RNA-seq
RNA sequencing, or RNA-Seq, is a high-throughput sequencing technology used to study the transcriptome of a cell. Transcriptomics helps to interpret the functional elements of a genome and identify the molecular constituents of an organism. Additionally, it also helps in understanding the development of an organism and the occurrence of diseases.
Before the discovery of RNA-seq, microarray-based methods and Sanger sequencing were used for transcriptome analysis. However, while microarray-based...
Before the discovery of RNA-seq, microarray-based methods and Sanger sequencing were used for transcriptome analysis. However, while microarray-based...


