microRNA是一類(lèi)內(nèi)源性的、非編碼RNA基因,。它通過(guò)與mRNA中特定的互補(bǔ)位點(diǎn)結(jié)合來(lái)調(diào)節(jié)蛋白編碼基因的表達(dá)和翻譯,，從而參與發(fā)育的精細(xì)調(diào)控等一系列重要的生命過(guò)程。眾所周知,，人類(lèi)群體在表型上的多樣性同群體和個(gè)體間基因表達(dá)的變異相關(guān),。而且，在基因組中,，不同基因的變異程度也有所不同,。前人的研究提示，在進(jìn)化過(guò)程中microRNA對(duì)基因表達(dá)的調(diào)控會(huì)使種間靶基因的表達(dá)差異小于其他基因的表達(dá)差異,，但在種內(nèi)是否如此尚不清楚,。
中科院昆明動(dòng)物所宿兵研究員的實(shí)驗(yàn)室最近通過(guò)對(duì)人群大腦基因表達(dá)譜的變異同microRNA調(diào)控關(guān)系的研究發(fā)現(xiàn)，microRNA對(duì)靶基因表達(dá)的調(diào)控會(huì)放大其表達(dá)變異,。通過(guò)對(duì)已發(fā)表的193例人類(lèi)大腦基因表達(dá)譜的分析發(fā)現(xiàn),，一個(gè)基因3’UTR區(qū)域包含的microRNA識(shí)別位點(diǎn)越多，則這個(gè)基因在人群中的表達(dá)譜變異越大,。這種相關(guān)性不受3’UTR長(zhǎng)度以及microRNA類(lèi)型的影響,。同時(shí),，研究結(jié)果還證明，人群中靶基因microRNA識(shí)別序列的變異也會(huì)導(dǎo)致表達(dá)譜的變異增加,。根據(jù)這些研究結(jié)果，他們提出,，種內(nèi)microRNA導(dǎo)致的基因組范圍的表達(dá)譜變異在進(jìn)化中可能有助于物種對(duì)環(huán)境的適應(yīng),，因?yàn)樗诨虮磉_(dá)水平提供了更寬廣的“緩沖帶”。此項(xiàng)研究結(jié)果將為我們更深入地了解microRNA對(duì)全基因組范圍內(nèi)蛋白質(zhì)基因的表達(dá)譜進(jìn)化所產(chǎn)生的影響提供嶄新的視角,。研究結(jié)果發(fā)表于國(guó)際知名生命科學(xué)刊物《核酸研究》（Nucleic Acids Research）上,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nucleic Acids Research，doi:10.1093/nar/gkn431,，Rui Zhang,，Bing Su
MicroRNA regulation and the variability of human cortical gene expression
Rui Zhang1,2,3 and Bing Su1,2,*
1State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, 2Kunming Primate Research Center, Chinese Academy of Sciences, Kunming 650223, China and 3Graduate School of Chinese Academy of Sciences, Beijing 100039, China
*To whom correspondence should be addressed. Tel: 86 871 5120202; Fax: 86 871 5193137; Email: [email protected]
Received May 5, 2008. Revised June 20, 2008. Accepted June 21, 2008.
Understanding the driving forces of gene expression variation within human populations will provide important insights into the molecular basis of human phenotypic variation. In the genome, the gene expression variability differs among genes, and at present, most research has focused on identifying the genetic variants responsible for the within population gene expression variation. However, little is known about whether microRNAs (miRNAs), which are small noncoding RNAs modulating expression of their target genes, could have impact on the variability of gene expression. Here we demonstrate that miRNAs likely lead to the difference of expression variability among genes. With the use of the genome-wide expression data in 193 human brain samples, we show that the increased variability of gene expression is concomitant with the increased number of the miRNA seeds interacting with the target genes, suggesting a direct influence of miRNA on gene expression variability. Compared with the non-miRNA-target genes, genes targeted by more than two miRNA seeds have increased expression variability, independent of the miRNA types. In addition, single-nucleotide polymorphisms (SNPs) located in the miRNA binding sites could further increase the gene expression variability of the target genes. We propose that miRNAs are one of the driving forces causing expression variability in the human genome.
