MicroRNAs可通过抑制一个信使RNA(mRNA)的转录或通过诱导其降解来调控基因表达。虽然以前的研究工作已经在mRNA层面上对这种调控进行了测量,但过去对有多少调控发生在蛋白层面上仍不知道。
现在,由David Bartel 和Nikolaus Rajewsky领导的两个小组,利用被称为SILAC(全称为“利用细胞培养中的氨基酸进行稳定同位素标记”)的方法的变通形式,对蛋白层面上所发生的蛋白组范围内的变化作为内生和外生microRNAs的表达的一个函数进行了测量。他们发现,虽然microRNAs能直接抑制数百个基因的转录,但更多的间接效应却能导致数千个基因的表达发生变化。然而,所观察到的很多变化在数量级上不到两倍,表明不管是直接还是间接,microRNAs都能充当“可变电阻器”,来微调蛋白合成,以便在任何一个给定的时间都能与细胞的需求相匹配。(生物谷Bioon.com)
生物谷推荐原始出处:
Nature 455, 58-63 (4 September 2008) | doi:10.1038/nature07228
Widespread changes in protein synthesis induced by microRNAs
Matthias Selbach1, Björn Schwanhäusser1,3, Nadine Thierfelder1,3, Zhuo Fang1, Raya Khanin2 & Nikolaus Rajewsky1
1 Max Delbrück Center for Molecular Medicine, Robert-R?ssle Str. 10, D-13125 Berlin, Germany
2 Department of Statistics, 15 University Gardens, University of Glasgow, Glasgow, G12 8QQ, UK
3 These authors contributed equally to this work.
Animal microRNAs (miRNAs) regulate gene expression by inhibiting translation and/or by inducing degradation of target messenger RNAs. It is unknown how much translational control is exerted by miRNAs on a genome-wide scale. We used a new proteomic approach to measure changes in synthesis of several thousand proteins in response to miRNA transfection or endogenous miRNA knockdown. In parallel, we quantified mRNA levels using microarrays. Here we show that a single miRNA can repress the production of hundreds of proteins, but that this repression is typically relatively mild. A number of known features of the miRNA-binding site such as the seed sequence also govern repression of human protein synthesis, and we report additional target sequence characteristics. We demonstrate that, in addition to downregulating mRNA levels, miRNAs also directly repress translation of hundreds of genes. Finally, our data suggest that a miRNA can, by direct or indirect effects, tune protein synthesis from thousands of genes.