生物谷报道:关闭特定基因表达是一种能力,这种能力不仅为研究细胞过程提供了一种有力的工具,而且也可用于癌症等疾病的治疗。本期Nature上两篇论文报告了关于用微小RNA(miRNAs)来进行基因沉默的研究结果。
微小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"(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.
原文出处:
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