Drosophila miR2 induces pseudo-polysomes and inhibits translation initiation
Drosophila miR2 induces pseudo-polysomes and inhibits translation initiation
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DOI：
10.1038/nature05878
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发表时间：
2007-06-14
期刊：
影响因子：
64.8
通讯作者：
Hentze, Matthias W.
中科院分区：
文献类型：
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作者：
Thermann, Rolf;Hentze, Matthias W.
MicroRNAs （miRs）抑制蛋白质合成的机制尚不清楚（1-11）。我们从黑腹果蝇胚胎中开发了一个无细胞系统，该系统通过黑腹果蝇死神信使RNA的39个未翻译区域忠实地再现了mir2介导的翻译控制。在这里，我们发现miR2抑制翻译起始而不影响mRNA的稳定性。令人惊讶的是，即使在多核糖体形成和60S核糖体亚基连接被阻断的情况下，miR2也能诱导致密（比80S重）mirnp（“伪多体”）的形成。携带ApppG而不是m(7) GpppG帽结构的mRNA逃脱了mir2介导的翻译块。这些结果直接表明抑制m(7) GpppG cap介导的翻译起始是miR2功能的机制，并揭示了可能有助于解释早期发现的伪多体信使核糖核蛋白组装。
MicroRNAs (miRs) inhibit protein synthesis by mechanisms that are as yet unresolved(1-11). We developed a cell-free system from Drosophila melanogaster embryos that faithfully recapitulates miR2-mediated translational control by means of the 39 untranslated region of the D. melanogaster reaper messenger RNA. Here we show that miR2 inhibits translation initiation without affecting mRNA stability. Surprisingly, miR2 induces the formation of dense ( heavier than 80S) miRNPs ('pseudo-polysomes') even when polyribosome formation and 60S ribosomal subunit joining are blocked. An mRNA bearing an ApppG instead of anm(7) GpppG cap structure escapes the miR2-mediated translational block. These results directly show the inhibition of m(7) GpppG cap-mediated translation initiation as the mechanism of miR2 function, and uncover pseudo-polysomal messenger ribonucleoprotein assemblies that may help to explain earlier findings.