用miRNAs进行基因沉默研究

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Nature：用miRNAs进行基因沉默研究 本期Nature上两篇论文报告了关于用微RNA（miRNAs）来进行基因沉默的研究结果。微RNA是指调控信使RNA稳定性和转录的小RNA。Chendrimada等人发现，三分子复合物RISC（该复合物已知能产生微RNA）与MOV10复合物发生相互作用，后者包括核糖体抗关联因子eIF6。这一发现表明，eIF6所起的作用是在演化过程中保留下来的、由微RNA引导的基因沉默的调控因子。RolfTherma

  生物谷报道： 本期Nature上两篇论文报告了关于用微RNA（miRNAs）来进行基因沉默的研究结果。微RNA是指调控信使RNA稳定性和转录的小RNA。Chendrimada等人发现，三分子复合物RISC（该复合物已知能产生微RNA）与MOV10复合物发生相互作用，后者包括核糖体抗关联因子eIF6。这一发现表明，eIF6所起的作用是在演化过程中保留下来的、由微RNA引导的基因沉默的调控因子。Rolf Thermann 和 Matthias Hentze发现，果蝇的微RNA“miR2”通过生成与核糖体非常相似的大miRNA复合物来阻止蛋白形成，而锁进所形成的“假多核糖体”中的信使RNA的作用便被有效阻止了。（引自Nature China）

英文原文:

Nature 447, 875-878 (14 July 2007) | doi:10.1038/nature05878; Received 7 November 2006; Accepted 26 April 2007; Published online 16 May 2007


Drosophila miR2 induces pseudo-polysomes and inhibits translation initiation
Rolf Thermann1 & Matthias W. Hentze1

European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany
Correspondence to: Matthias W. Hentze1 Correspondence and requests for materials should be addressed to M.W.H. (Email: hentze@embl.de).


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MicroRNAs (miRs) inhibit protein synthesis by mechanisms that are as yet unresolved1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11. We developed a cell-free system from Drosophila melanogaster embryos that faithfully recapitulates miR2-mediated translational control by means of the 3' 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 an m7GpppG cap structure escapes the miR2-mediated translational block. These results directly show the inhibition of m7GpppG cap-mediated translation initiation as the mechanism of miR2 function, and uncover pseudo-polysomal messenger ribonucleoprotein assemblies that may help to explain earlier findings.