生物谷報道:關閉特定基因表達是一種能力,這種能力不僅為研究細胞過程提供了一種有力的工具,,而且也可用于癌癥等疾病的治療,。本期Nature上兩篇論文報告了關于用微小RNA(miRNAs)來進行基因沉默的研究結果。
微小RNA是指調控信使RNA穩(wěn)定性和轉錄的小RNA,。Chendrimada等人發(fā)現(xiàn),,三分子復合物RISC(該復合物已知能產生微RNA)與MOV10復合物發(fā)生相互作用,后者包括核糖體抗關聯(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引導的基因沉默的調控因子,。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復合物來阻止蛋白形成,而鎖進所形成的"假多核糖體"(pseudo-polysome)中的信使RNA的作用便被有效阻止了,。
FIGURE 1. Biochemical and functional analysis of eIF6 in the miRNA pathway.
a, b, Flag affinity eluate was fractionated on a Superose 6 gel filtration medium after which the column fractions were subjected to SDS–PAGE and either silver staining or western blot analysis. Fractions of the column are denoted on the top and molecular mass markers are indicated at the bottom. Asterisks denote contaminating polypeptides. c, Illustration of Renilla luciferase containing the wild-type or mutant let-7b sites. d, Reporter constructs containing one or two let7-b-responsive sites are repressed in HeLa cells. e, f, Treatment with 2'-O-methyl single-stranded RNA (let-7b as) or eIF6 knockdown abolishes let-7b-mediated translational repression without any effect on reporters with a mutant let-7b binding site. Each point represents at least three independent experiments. Error bars in d–f indicate s.e.m.
原文出處:
Nature Volume 447 Number 7146
MicroRNA silencing through RISC recruitment of eIF6 p823
Thimmaiah P. Chendrimada, Kenneth J. Finn, Xinjun Ji, David Baillat, Richard I. Gregory, Stephen A. Liebhaber, Amy E. Pasquinelli & Ramin Shiekhattar
doi:10.1038/nature05841
Abstract | Full Text | PDF (2,149K) | Supplementary information
See also: Editor's summary
Drosophila miR2 induces pseudo-polysomes and inhibits translation initiation p875
Rolf Thermann & Matthias W. Hentze
doi:10.1038/nature05878
First paragraph | Full Text | PDF (340K) | Supplementary information
See also: Editor's summary