microRNA是一类内源性的、非编码RNA基因。它通过与mRNA中特定的互补位点结合来调节蛋白编码基因的表达和翻译，从而参与发育的精细调控等一系列重要的生命过程。众所周知，人类群体在表型上的多样性同群体和个体间基因表达的变异相关。而且，在基因组中，不同基因的变异程度也有所不同。前人的研究提示，在进化过程中microRNA对基因表达的调控会使种间靶基因的表达差异小于其他基因的表达差异，但在种内是否如此尚不清楚。
中科院昆明动物所宿兵研究员的实验室最近通过对人群大脑基因表达谱的变异同microRNA调控关系的研究发现，microRNA对靶基因表达的调控会放大其表达变异。通过对已发表的193例人类大脑基因表达谱的分析发现，一个基因3’UTR区域包含的microRNA识别位点越多，则这个基因在人群中的表达谱变异越大。这种相关性不受3’UTR长度以及microRNA类型的影响。同时，研究结果还证明，人群中靶基因microRNA识别序列的变异也会导致表达谱的变异增加。根据这些研究结果，他们提出，种内microRNA导致的基因组范围的表达谱变异在进化中可能有助于物种对环境的适应，因为它在基因表达水平提供了更宽广的“缓冲带”。此项研究结果将为我们更深入地了解microRNA对全基因组范围内蛋白质基因的表达谱进化所产生的影响提供崭新的视角。研究结果发表于国际知名生命科学刊物《核酸研究》（Nucleic Acids Research）上。（生物谷Bioon.com）
生物谷推荐原始出处：
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: sub@mail.kiz.ac.cn
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.
