毒素缺乏会通过核核ncRNA驱动的蛋白质聚合来破坏蛋白质稳定
Xuemei Wen1, Hengyi Xu1, Phillip R Woolley1
1Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
The Journal of cell biology
|May 8, 2024
概括
丢失的Senataxin,一个RNA-DNA螺旋酶,导致核中的蛋白质聚合. 这与R环积累和非编码RNA有关,影响蛋白质稳态和神经退行性疾病研究.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 神经科学是一个神经科学.
背景情况:
- 参毒素是一种RNA-DNA基酶,对DNA修复和转录终止至关重要.
- 毒素功能障碍与人类的神经退行性疾病有关.
- 之前的研究表明,R循环会导致DNA损伤和蛋白质聚合.
研究的目的:
- 为了研究Senataxin损失对蛋白质平衡的影响.
- 为了确定是否Senataxin缺乏导致蛋白质聚合.
- 为了确定细胞的位置和聚合物形成的机制.
主要方法:
- 在Senataxin缺乏细胞中分析蛋白质溶解度.
- 使用分子技术绘制RNA-DNA混合 (R-loop) 位点的地图.
- 研究非编码RNA在聚合物形成中的作用.
- 蛋白质聚合物的细胞和亚细胞局部化研究.
主要成果:
- 毒素损失导致不溶性蛋白质的积累,许多与神经退行性疾病有关.
- 蛋白质聚合物主要存在于细胞核中.
- 在核糖体DNA和周中心区域增加R环积累,而不是蛋白质编码基因.
- 来自核糖体DNA的非编码RNA的升级促进了聚合物的形成.
结论:
- 毒素缺乏会通过转录依赖性病变破坏蛋白质组的溶解性.
- 细胞核是塞纳素损失引起的蛋白质聚合的关键部位.
- 研究结果提供了关于神经退行症与塞纳素功能障碍相关的分子机制的见解.
相关概念视频
Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
The Proteasome
830
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
830
Translation
141.9K
Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of...
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of...
141.9K
The Nucleolus
8.8K
The nucleolus is the most prominent substructure of the nucleus. When it was first discovered, it was considered to be an isolated organelle that forms fibrils and granules. In 1931, the relationship between the nucleolus and chromosomes was first described by Heitz. He observed that the appearance and size of nucleolus varies depending on the stage of the cell cycle. He also noticed constricted regions on different chromosomes clustered together at definite cell cycle stages. These regions,...
8.8K
Nucleosome Remodeling
9.1K
Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
9.1K
Nonsense-mediated mRNA Decay
10.6K
The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
10.6K


