人类卵子中的Codon组成揭示了mRNA衰变中的与年龄相关的缺陷
Pavla Brachova1, Lane K Christenson2, Nehemiah S Alvarez1,3
1Department of Biomedical and Translational Sciences, Division of Woman and Child Health, Eastern Virginia Medical School, Macon and Joan Brock Virginia Health Sciences, Old Dominion University, Norfolk, VA 23518, USA.
International journal of molecular sciences
|October 16, 2025
概括
生殖衰老改变了人类卵细胞中信使RNA (mRNA) 稳定性的控制方式,这可能会影响生育能力. 这种与年龄相关的转变可能导致某些mRNAs的积累,影响早期胚胎发育.
科学领域:
- 生殖生物学 生殖生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 卵细胞发育潜力随着发育年龄的增长而下降.
- 与年龄相关的卵细胞功能障碍背后的机制尚未完全理解.
- 卵细胞成熟依赖于母体mRNA的翻译控制.
研究的目的:
- 研究人类卵子细胞的生殖衰老如何影响母亲的mRNA稳定性和翻译.
- 为了确定mRNA序列稳定关系的年龄相关变化.
- 探索这些变化对卵细胞能力和早期胚胎发育的影响.
主要方法:
- 来自30岁以下女性的人类卵子细胞的计算分析与40岁以上女性的计算分析.
- 检查mRNA的GC含量,半衰期和蛋白质丰度.
- 分析编码子组成及其对卵细胞成熟期间mRNA稳定性的影响 (GV到MII过渡).
主要成果:
- mRNA GC含量与年轻卵子的半衰期相反相关,但与老卵子的半衰期相反相关.
- 在老化的卵细胞中,GC含量与蛋白质丰富度正相关.
- 生殖衰老改变了代码子的最佳性,有利于富含GC的代码子和稳定特定的母性mRNA.
- 随着年龄的增长,在GV-MII过渡期间发生GC稳定性关联的逆转.
结论:
- 生殖衰老对人类卵细胞的翻译合mRNA衰变途径进行重新编程.
- 老化的卵细胞可能会稳定富含GC的母性mRNA,从而导致成熟期间潜在的过度转化.
- 在老化的卵细胞中破坏mRNA清除可以损害卵细胞的能力,并影响母亲的mRNA剂量,影响胚胎发育.
相关概念视频
02:27Nonsense-mediated mRNA Decay
11.7K
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,...
11.7K
02:27Nonsense-mediated mRNA Decay
3.3K
3.3K
02:31Nuclear Export of mRNA
8.7K
Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
8.7K
02:31Nuclear Export of mRNA
5.2K
5.2K
02:07Oogenesis
69.0K
In human women, oogenesis produces one mature egg cell or ovum for every precursor cell that enters meiosis. This process differs in two unique ways from the equivalent procedure of spermatogenesis in males. First, meiotic divisions during oogenesis are asymmetric, meaning that a large oocyte (containing most of the cytoplasm) and minor polar body are produced as a result of meiosis I, and again following meiosis II. Since only oocytes will go on to form embryos if fertilized, this unequal...
69.0K
02:51mRNA Stability and Gene Expression
3.4K
3.4K