MicroRNA regulation and the variability of human cortical gene expression.

MicroRNA regulation and the variability of human cortical gene expression.
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MicroRNA 调控和人类皮质基因表达的变异性

DOI:
10.1093/nar/gkn431
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发表时间:
2008-08
影响因子:
14.9
通讯作者:
Su B
Su B
中科院分区:
生物学2区
文献类型:
--
作者:
Zhang R;Su B

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了解人类基因表达变异的驱动力将为了解人类表型变异的分子基础提供重要的见解。在基因组中,基因表达变异因基因而异,目前大多数研究都集中于识别导致群体内基因表达变异的遗传变异。然而,人们对 microRNA (miRNA) 这种调节靶基因表达的小非编码 RNA 是否会对基因表达的变异性产生影响知之甚少。在这里,我们证明 miRNA 可能导致基因之间表达变异性的差异。通过使用 193 个人脑样本的全基因组表达数据,我们发现基因表达变异性的增加伴随着与靶基因相互作用的 miRNA 种子数量的增加,这表明 miRNA 对基因表达变异性有直接影响。与非 miRNA 靶基因相比,两个以上 miRNA 种子靶向的基因具有增加的表达变异性,与 miRNA 类型无关。此外,位于miRNA结合位点的单核苷酸多态性(SNP)可以进一步增加靶基因的基因表达变异性。我们认为 miRNA 是导致人类基因组表达变异的驱动力之一。
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.
DOI: 10.1126/science.1064921
发表时间: 2001-10-26
期刊: SCIENCE
影响因子: 56.9
作者:
Lagos-Quintana, M;Rauhut, R;Tuschl, T
通讯作者: Tuschl, T
DOI: 10.1186/gb-2004-5-10-r80
发表时间: 2004
期刊: Genome biology
影响因子: 12.3
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发表时间: 2005-02-18
期刊: SCIENCE
影响因子: 56.9
作者:
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通讯作者: Cox, DR
DOI: 10.1126/science.1121158
发表时间: 2005-12-16
期刊: SCIENCE
影响因子: 56.9
作者:
Farh, KKH;Grimson, A;Bartel, DP
通讯作者: Bartel, DP
DOI: 10.1126/science.1122689
发表时间: 2006-04-07
期刊: SCIENCE
影响因子: 56.9
作者:
Giraldez, AJ;Mishima, Y;Schier, AF
通讯作者: Schier, AF