在遭受压力的人类细胞中缓解微RNA介导的转化抑制
Suvendra N Bhattacharyya1, Regula Habermacher, Ursula Martine
1Friedrich Miescher Institute for Biomedical Research, P.O. Box 2543, 4002 Basel, Switzerland.
Cell
|June 17, 2006
概括
基因表达的微RNA抑制是可逆的. 压力条件可以从miR-122抑制中释放cationic氨基酸载体1 (CAT-1) mRNA,恢复蛋白质的产生.
科学领域:
- 分子生物学分子生物学
- 基因法规 基因法规
- 在RNA生物学,RNA生物学.
背景情况:
- 微RNAs (miRNAs) 是元动物中基因表达的关键调节者.
- miRNAs通常与目标mRNA的3'未翻译区域 (3'UTR) 结合,抑制蛋白质合成或促进mRNA衰变.
- 微RNA介导抑制的可逆性在很大程度上仍未被探索.
研究的目的:
- 调查miRNA诱导的基因沉默是否是一种可逆的过程.
- 确定潜在的目标mRNAs脱抑制的潜在机制.
- 检查压力条件在调节miRNA活动中的作用.
主要方法:
- 使用了人类肝癌细胞.
- 研究了miR-122.2.通过氨基酸载体1 (CAT-1) mRNA的调节.
- 雇佣的记者测试来评估基因表达.
- 研究了mRNA和蛋白质相互作用的亚细胞局部化,使用诸如多体造型和RNA结合蛋白质分析等技术.
主要成果:
- 证明miR-122诱导的CAT-1mRNA及其3'UTR记者抑制在压力条件下是可逆的.
- 观察到,去压缩的CAT-1mRNA从处理体中释放出来,并被招募到多元体中.
- 表明HuR (富AU元素结合蛋白) 与CAT-1 3'UTR的结合对于这种放压过程至关重要.
结论:
- 通过miRNA介导的基因抑制并不总是永久的状态,并且可以逆转.
- 压力诱导的特定mRNAs的减压包括从抑制复合物释放和随后的翻译.
- 与3'UTR相互作用的HuR等蛋白质可以调节miRNA的有效性,这表明在基因表达控制中起着更广泛的作用.
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