生物谷報(bào)道: 本期Nature上兩篇論文報(bào)告了關(guān)于用微RNA(miRNAs)來進(jìn)行基因沉默的研究結(jié)果,。微RNA是指調(diào)控信使RNA穩(wěn)定性和轉(zhuǎn)錄的小RNA。Chendrimada等人發(fā)現(xiàn),,三分子復(fù)合物RISC(該復(fù)合物已知能產(chǎn)生微RNA)與MOV10復(fù)合物發(fā)生相互作用,,后者包括核糖體抗關(guān)聯(lián)因子eIF6。這一發(fā)現(xiàn)表明,,eIF6所起的作用是在演化過程中保留下來的,、由微RNA引導(dǎo)的基因沉默的調(diào)控因子。Rolf Thermann 和 Matthias Hentze發(fā)現(xiàn),,果蠅的微RNA“miR2”通過生成與核糖體非常相似的大miRNA復(fù)合物來阻止蛋白形成,,而鎖進(jìn)所形成的“假多核糖體”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: [email protected]).
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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.