在线粒分裂过程中,核聚甲结合蛋白 (PABPN1) 的酸化保护mRNA免受超化,并维持转录组动态
Jackson M Gordon1, David V Phizicky1, Leonard Schärfen1
1Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
Nucleic acids research
|June 29, 2024
概括
核PABPN1由线粒激酶的酸化调节了mRNA动态. 抑制突变会损害细胞增殖,而模仿突变会改变多 (A) 尾长和mRNA循环.
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 生物化学
背景情况:
- 多基解对于mRNA处理,出口,翻译和衰变至关重要.
- 多A结合蛋白 (PABPs) 协调这些mRNA生命周期事件.
- 对PABP,特别是核PABP1的监管仍然不完全理解.
研究的目的:
- 为了研究人类核 PABPN1 在转化过程中的调节.
- 确定PABPN1酸化对mRNA动态和细胞增殖的功能影响.
主要方法:
- 局部定向突变生成以产生阻和模仿性PABPN1突变.
- 稳定的细胞系产生用于诱导蛋白质表达.
- 长读测序和TimeLapse-seq用于分析多个A) 尾巴长度,mRNA合成和衰变.
主要成果:
- 在线粒分裂过程中,PABPN1在四个部位被线粒激酶酸化.
- 抑制性PABPN1突变体降低了细胞增殖.
- 突变者表现出改变的多A尾巴长度,抑制突变者延长了尾巴,模仿突变者缩短了它们,增加了非A核酸.
- 模仿性PABPN1增加了转录,并降低了特定mRNA的稳定性.
结论:
- PABPN1的线性酸化对细胞增殖至关重要.
- PABPN1酸化动态地重塑了多A尾部,并影响了mRNA的循环.
- 这些发现支持一个模型,其中细胞周期依赖的转录组动态通过PABPN1调节被重置.
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