酵母多A结合蛋白 (Pab1) 在体内控制翻译启动,主要通过阻断mRNA分解和衰变来控制翻译启动
Poonam Poonia1, Vishalini Valabhoju1, Tianwei Li2
1Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, United States.
Nucleic acids research
|March 12, 2025
概括
聚A结合蛋白 (Pab1) 枯竭会降低mRNA和蛋白质水平,影响翻译. 这种效应在很大程度上是由mRNA分解和降解,特别是对于基因表达的基因表达介导的.
科学领域:
- 分子生物学分子生物学
- 酵母遗传学 酵母遗传学
- 转录后条例 转录后条例 转录后条例
背景情况:
- 聚A结合蛋白 (Pab1) 在mRNA衰变和翻译启动中起着至关重要的作用.
- 在Pab1的功能背后的精确分子机制仍然不完全理解.
研究的目的:
- 阐明Pab1在mRNA调节和翻译中的分子功能.
- 研究Pab1,mRNA衰变途径和转化控制之间的相互作用.
主要方法:
- 使用辅酶诱导降解来耗尽Pab1在野生类型酵母和一个切割酶突变 (dcp2Δ).
- 分析散装mRNA的丰度,多体形状和多个A的尾巴长度.
- 评估各种mRNA的转化效率 (TE).
- 研究基因表达调节的基因表达调节.
主要成果:
- 在野生类型细胞中,Pab1耗尽减少了mRNA和多体丰度,但在dcp2Δ突变体中没有,这表明增强了切割/降解.
- 在dcp2Δ突变体中,在Pab1耗尽时,多A尾长的增加不存在,这表明短尾mRNAs的偏好切割.
- 在dcp2Δ细胞中,转化效率的变化减少,突出显示了mRNA丰度在转化重编程中的作用.
- 在Pab1耗尽后,基因组mRNA和蛋白质以切割依赖的方式被特别减少,与密码促进体激活相关.
结论:
- 增强的mRNA切割和降解是Pab1水平限制时翻译减少的主要驱动因素.
- 帕布1涉及到组织基因表达的转录后控制,影响核细胞体占用率.
- 闭环mRNP模型涉及PABP-eIF4G相互作用,在正常情况下对于大多数转录来说并不必不可少.
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