西亚试剂：MicroRNA regulation and the variability of human cortical g

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: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 (s), 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.

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