MicroRNAs可通過抑制一個信使RNA（mRNA）的轉(zhuǎn)錄或通過誘導(dǎo)其降解來調(diào)控基因表達(dá),。雖然以前的研究工作已經(jīng)在mRNA層面上對這種調(diào)控進(jìn)行了測量,，但過去對有多少調(diào)控發(fā)生在蛋白層面上仍不知道。
現(xiàn)在,，由David Bartel 和Nikolaus Rajewsky領(lǐng)導(dǎo)的兩個小組,，利用被稱為SILAC（全稱為“利用細(xì)胞培養(yǎng)中的氨基酸進(jìn)行穩(wěn)定同位素標(biāo)記”）的方法的變通形式，對蛋白層面上所發(fā)生的蛋白組范圍內(nèi)的變化作為內(nèi)生和外生microRNAs的表達(dá)的一個函數(shù)進(jìn)行了測量,。他們發(fā)現(xiàn),，雖然microRNAs能直接抑制數(shù)百個基因的轉(zhuǎn)錄，但更多的間接效應(yīng)卻能導(dǎo)致數(shù)千個基因的表達(dá)發(fā)生變化,。然而,，所觀察到的很多變化在數(shù)量級上不到兩倍，表明不管是直接還是間接,，microRNAs都能充當(dāng)“可變電阻器”,，來微調(diào)蛋白合成，以便在任何一個給定的時間都能與細(xì)胞的需求相匹配。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
