RNA结合蛋白Pub1调节含有上游开放阅读框架的转录的稳定性
M J Ruiz-Echevarría1, S W Peltz
1Department of Molecular Genetics and Microbiology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway 08854, USA. ruizeche@umdnj.edu
Cell
|July 13, 2000
概括
无意中介衰变 (NMD) 针对具有上游开放阅读框架 (uORF) 的转录. 然而,一些mRNA中的稳定元件 (STE) 与Pub1蛋白相互作用,防止NMD,调节基因表达.
科学领域:
- 分子生物学分子生物学
- 在RNA生物学,RNA生物学.
- 基因法规 基因法规
背景情况:
- 无意义介导的mRNA衰变 (NMD) 途径通过过早停止编码子降解转录.
- 在5'-未翻译区域的上游开放阅读框架 (uORF) 可以触发NMD,但一些转录可以逃避这种退化.
- 了解uORF含有的转录中NMD耐药性的机制对于基因调节至关重要.
研究的目的:
- 研究某些含有uORF的mRNA抵抗NMD.的机制.
- 识别调节转录的稳定性的因素与uORFs.
- 阐明RNA结合蛋白Pub1在NMD调节中的作用.
主要方法:
- 分析GCN4,YAP1和CPA1的mRNA序列和结构.
- 研究稳定剂元素 (STE) 与RNA结合蛋白之间的相互作用 Pub1.
- 评估STE和Pub1对NMD路径活动的影响.
主要成果:
- 含有 uORF 的 GCN4 和 YAP1 mRNA 具有稳定元件 (STE).
- 该STE与RNA结合蛋白Pub1相互作用,使其对NMD产生抗性.
- 缺乏STE的CPA1mRNA被NMD途径降解,突出显示了STE在转录稳定中的作用.
结论:
- 上游开放阅读框架 (uORF) 是翻译和mRNA周转的关键调节器.
- 稳定元件 (STE) 和它与Pub1的相互作用是含有uORF的转录中NMD抗性的关键决定因素.
- Pub1是调节含有uORF的mRNA稳定的关键因素,影响基因表达调节.
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