异黄素对氨酸的替代支持在异黄素剥夺期间的细胞生理学
Gautam Kok1, Imre F Schene1, Eveline F Ilcken1
1Department of Metabolic Diseases, Wilhelmina Children's Hospital, University Medical Center Utrecht, Lundlaan 6, 3584 EA Utrecht, The Netherlands.
Nucleic acids research
|December 10, 2024
概括
在缺少异黄素时,细胞将氨酸纳入蛋白质中,这是维持翻译和细胞功能至关重要的过程. 这突出了在氨基酸短缺期间保护翻译速度而不是准确性的一般机制.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生化学
背景情况:
- 氨基酸-tRNA合成酶 (ARSs) 是关键的酶,它们将特定的氨基酸附着在它们的同类tRNA上.
- 虽然ARS表现出高特异性,但它们可以与结构相似的氨基酸误导tRNA,从而需要编辑功能.
- 单氨酸 (Ile) 和氨酸 (Val) 是结构相似的氨基酸,对单氨酸-tRNA合成酶1 (IARS1) 构成潜在的挑战.
研究的目的:
- 为了研究限制异黄素对人类纤维细胞蛋白质合成的影响.
- 为了确定氨酸错误纳入在维持细胞功能在缺异黄素条件下的作用.
- 探索细胞在局部氨基酸稀缺期间维持翻译的补偿机制.
主要方法:
- 使用双光记者系统来监测蛋白质翻译动态.
- 在不同度的异黄素和氨酸下将量化氨基酸纳入蛋白质.
- 评估了isoleucine剥夺和氨酸补充的救援在野生类型和IARS1缺乏细胞中的抗增殖作用.
主要成果:
- 健康的纤维细胞在isoleucine枯竭期间在isoleucine密码子中加入了氨酸,这种减少是由野生型IARS1.1介导的.
- 氨酸补充物完全挽救了健康细胞中因异黄素缺乏而引起的翻译和细胞增殖缺陷.
- 观察到异黄素与氨酸的替代物可以防止转化终止并保持细胞功能.
结论:
- 细胞在缺少异黄素时采用一种将氨酸纳入异黄素的机制,以保持转化忠实性和细胞活力.
- 这种由IARS1引起的补偿性错化对于在营养压力下维护蛋白质合成和细胞功能至关重要.
- 这代表了一个更广泛的哺乳动物细胞战略,在面对局部氨基酸限制时,优先考虑翻译速度和功能而不是绝对忠实.
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