MicroRNAs control translation initiation by inhibiting eukaryotic initiation factor 4E/cap and poly(A) tail function
MicroRNAs control translation initiation by inhibiting eukaryotic initiation factor 4E/cap and poly(A) tail function
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DOI：
10.1073/pnas.0506482102
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发表时间：
2005-11-22
影响因子：
11.1
通讯作者：
Preiss, T
中科院分区：
文献类型：
--
作者：
Humphreys, DT;Westman, BJ;Preiss, T
MicroRNAs （miRNAs）通过与3' UTR中部分不匹配的序列相互作用来抑制目标mrna的翻译。它们作用于翻译的机制在很大程度上仍然不清楚。我们在共转染同源miRNA的HeLa细胞中检测了3' UTR中含有四个部分不匹配的miRNA结合位点的mrna的翻译。这些mrna是通过体外转录制备的，并被设计成采用不同的翻译起始模式。我们发现5‘帽结构和3’ poly(A) tail对于mirna介导的mRNA翻译的完全抑制都是必要的，但不是充分的。用蟋蟀麻痹病毒或脑心肌炎病毒的内部核糖体进入位点替代帽状结构会损害mirna介导的抑制。总之，这些结果表明，mirna干扰翻译的起始步骤，并暗示帽结合蛋白真核起始因子4E是一个分子靶标。
MicroRNAs (miRNAs) repress translation of target mRNAs by interaction with partially mismatched sequences in their 3' UTR. The mechanism by which they act on translation has remained largely obscure. We examined the translation of mRNAs containing four partially mismatched miRNA-binding sites in the 3' UTR in HeLa cells cotransfected with a cognate miRNA. The mRNAs were prepared by in vitro transcription and were engineered to employ different modes of translation initiation. We find that the 5' cap structure and the 3' poly(A) tail are each necessary but not sufficient for full miRNA-mediated repression of mRNA translation. Replacing the cap structure with an internal ribosome entry site from either the cricket paralysis virus or the encephalomyocarditis virus impairs miRNA-mediated repression. Collectively, these results demonstrate that miRNAs interfere with the initiation step of translation and implicate the cap-binding protein eukaryotic initiation factor 4E as a molecular target.