The mechanism of micro-RNA-mediated translation repression is determined by the promoter of the target gene
The mechanism of micro-RNA-mediated translation repression is determined by the promoter of the target gene
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DOI：
10.1073/pnas.0800650105
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发表时间：
2008-07-01
影响因子：
11.1
通讯作者：
Bushell, Martin
中科院分区：
文献类型：
--
作者：
Kong, Yi Wen;Cannell, Ian G.;Bushell, Martin
微小RNA（miRNAs）是与靶mRNA中同源区域不完全碱基配对的非编码RNA。并对相应蛋白质的合成产生负面影响。抑制由许多机制介导，其中之一是直接抑制蛋白质合成。令人惊讶的是，以前的研究表明，存在两种相互排斥的机制，一种作用于蛋白质合成的起始阶段，另一种作用于起始后事件。在这里，我们解决这个明显的二分法，证明用于转录mRNA的启动子影响类型的miRNA介导的翻译抑制。在其3'UTR中含有let-7靶位点的来自SV 40启动子的转录物在翻译的起始阶段被抑制，而来自TK启动子的基本相同的mRNA在后起始步骤被抑制。我们还表明，在c-myc mRNA的3' UTR内存在miR-34靶位点，并且启动子依赖性也适用于该内源性3' UTR。总的来说，这些数据建立了mRNA的核历史和细胞质中miRNA介导的翻译调控机制之间的联系。
MicroRNAs (miRNAs) are noncoding RNAs that base pair imperfectly to homologous regions in target mRNAs. and negatively influence the synthesis of the corresponding proteins. Repression is mediated by a number of mechanisms, one of which is the direct inhibition of protein synthesis. Surprisingly, previous studies have suggested that two mutually exclusive mechanisms exist, one acting at the initiation phase of protein synthesis and the other at a postinitiation event. Here, we resolve this apparent dichotomy by demonstrating that the promoter used to transcribe the mRNA influences the type of miRNA-mediated translational repression. Transcripts derived from the SV40 promoter that contain let-7 target sites in their 3' UTRs are repressed at the initiation stage of translation, whereas essentially identical mRNAs derived from the TK promoter are repressed at a postinitiation step. We also show that there is a miR-34 target site within the 3' UTR of c-myc mRNA and that promoter dependency is also true for this endogenous 3' UTR. Overall, these data establish a link between the nuclear history of an mRNA and the mechanism of miRNA-mediated translational regulation in the cytoplasm.