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5' UTR m(6) A 促进上限独立的翻译
Kate D Meyer1, Deepak P Patil1, Jun Zhou2
1Department of Pharmacology, Weill Medical College, Cornell University, New York, NY 10065, USA.
Cell
|November 24, 2015
概括
传递 RNA (mRNA) 的翻译可以独立于 5' 盖. 在5'非转化区域 (UTR) 中的N(6) -甲基氨酸 (m(6) 直接调用转化机制,特别是在细胞应激过程中.
科学领域:
- 分子生物学
- 核糖核酸生物学
- 基因表达的调节
背景情况:
- 蛋白质翻译通常通过5'盖的识别由盖结合复合体启动.
- 不依赖上限的翻译机制尚不清楚.
- 甲基氨酸 (m(6) 是一种普遍存在的mRNA修饰.
研究的目的:
- 调查5' UTR m(6) A在上限独立转换中的作用.
- 阐明5' UTR m(6) A促进翻译的机制.
- 在细胞应激过程中确定这种机制的意义.
主要方法:
- 在5' UTR中引入或删除m(6) A的位点定向突变.
- 生物化学测定以评估真核启动因子3 (eIF3) 与m(6) A的结合.
- 在体外翻译试验.
- 在热冲击后对Hsp70mRNA翻译的分析.
- 在各种压力条件下进行转录组范围的分析.
主要成果:
- 在5' UTR中单个m(6) A足以调解顶部独立转换.
- 5' UTR m(6) A直接与eIF3结合,促进了43S核糖体复合体的招募.
- 抑制腺甲基化特别影响5' UTR m(6) A含有的mRNA的翻译.
- 热冲击诱导Hsp70mRNA中的m(6) A水平增加,促进其独立于帽子的翻译.
- 细胞应力导致m(6) A的全球再分配,增加5' UTR m(6) A的修饰.
结论:
- 5' UTR m(6) 通过直接使用eIF3来实现上限独立的翻译启动.
- 在细胞应激条件下,这种途径提供了选择性mRNA转换的机制.
- 在应激反应过程中,m(6) A修饰作用为基因表达的调节开关.
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