通过FXR1和Argonaute 2进行转换的AU富元素介导上调调节
Shobha Vasudevan1, Joan A Steitz
1Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06536, USA.
Cell
|March 27, 2007
概括
富含AU的元素 (AREs) 调节基因表达. 研究人员发现,脆弱的X-精神延迟相关蛋白1 (FXR1) 和阿尔戈诺特2 (AGO2) 在细胞生长停止期间激活含有ARE的mRNA的翻译.
科学领域:
- 分子生物学分子生物学
- 基因规则 基因规则
- 转录后控制 转录后控制
背景情况:
- 在mRNA 3'-UTR中的富含AU元素 (AREs) 是mRNA稳定性和翻译的关键调节者.
- 激增性抗原体影响基因表达,具有显著的临床和发育影响.
- 特别地,TNFalpha ARE在血清饥饿诱导的细胞循环停止期间增强了翻译.
研究的目的:
- 在翻译激活条件下识别与ARE相关的蛋白质.
- 调查已识别的蛋白质在ARE介导的翻译控制中的作用.
- 阐明ARE信号与微RNP相关蛋白之间的相互作用.
主要方法:
- 开发一种 in vivo 交叉连接合的亲和力净化方法.
- 在基底和活性翻译条件下分离和分析ARE相关复合物.
- 连接试验和shRNA-knockdown实验以评估蛋白质功能.
主要成果:
- 与脆弱X-精神延迟相关的蛋白1 (FXR1) 和阿尔戈诺特2 (AGO2) 被确定为新型ARE结合蛋白.
- FXR1 和 AGO2 仅在翻译激活过程中与 AREs 关联.
- 直接证据证实了FXR1和AGO2的翻译激活功能,突出了它们的相互依赖.
结论:
- FXR1和AGO2在细胞生长依赖的ARE含有mRNA的翻译激活中起着至关重要的作用.
- 这一发现揭示了ARE介导的信号与微型RNP相关的监管系统之间的新联系.
- 这项研究为管理转录后基因调节的复杂机制提供了新的见解.
相关概念视频
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01:31Translation
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