ERC积累使rDNA中的Sir2耗尽,并通过rDNA的破坏稳定诱导细胞衰老
Yoshio Yamamuro1,2, Yuta Uneme1,2, Sihan Li3
1Laboratory of Genome Regeneration, Institute for Quantitative Biosciences (IQB), The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Nucleic acids research
|October 29, 2025
概括
基因组不稳定导致细胞衰老. 在老酵母细胞中,在E-pro区域增加的组素乙化触发了核糖体DNA (rDNA) 的不稳定性,缩短了寿命.
科学领域:
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
- 衰老研究研究 衰老研究
背景情况:
- 基因组不稳定是细胞衰老和衰老的关键驱动因素.
- 核糖体DNA (rDNA) 是一个特别不稳定的基因组区域,其不稳定性有助于缩短发芽酵母的寿命.
- 衰老细胞中rDNA不稳定的确切机制在很大程度上是未知的.
研究的目的:
- 为了阐明驱动老年芽发酵母细胞中的核糖体DNA (rDNA) 不稳定性的分子机制.
- 调查非编码RNA转录和基因组修饰在衰老过程中rDNA不稳定性中的作用.
主要方法:
- 隔离旧的芽酵母细胞.
- 来自E-pro促进体的非编码RNA转录的分析.
- 在rDNA位点评估基因素乙化水平 (H3K14和H4K16).
- 研究Gcn5和Sir2在rDNA稳定性和E-pro转录中的作用.
- 额外染色体rDNA循环 (ERC) 的量化.
主要成果:
- 在老细胞中,来自E-pro促进体的非编码RNA转录增加,与H3K14和H4K16乙化升高相关.
- Gcn5的耗尽减少了E-pro转录,并减轻了rDNA的不稳定性.
- 随着年龄的增长,Sir2水平并没有下降,但观察到它从染色体rDNA中耗尽.
- 染色体外rDNA循环 (ERC) 的积累与染色体rDNA的Sir2耗尽有关.
结论:
- 从E-pro驱动的基因组乙化增加和随后的非编码RNA转录导致老酵母的rDNA不稳定.
- 由ERC积累引起的rDNA的Sir2耗尽是与衰老相关的rDNA不稳定性的关键因素.
- 提出了一个新型的发芽酵母衰老模型,涉及Sir2枯竭和rDNA不稳定性.
相关概念视频
02:15Replicative Cell Senescence
4.3K
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
4.3K
02:36DNA Damage can Stall the Cell Cycle
10.0K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
10.0K
02:36DNA Damage Can Stall the Cell Cycle
3.0K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
3.0K
01:23Negative Regulator Molecules
38.2K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
38.2K
02:23Abnormal Proliferation
5.1K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.1K
02:15Experimental RNAi
7.2K
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
7.2K