microRNA expression levels in human primary fibroblasts

MicroRNAs (miRNAs) are regulatory non-coding RNAs that affect the production of a significant fraction of human mRNAs via post-transcriptional regulation. Inter-individual variation of miRNA expression levels is likely to influence the expression of miRNA target genes, and may therefore contribute to phenotypic differences in humans, including susceptibility to common disorders. The extent to which miRNA levels are genetically controlled is largely unknown. In this report, we assayed the expression levels of miRNAs in primary fibroblasts from 180 European newborns of the GenCord project, and performed association analysis to identify eQTLs (expression quantitative traits loci). We detected robust expression for 121 miRNAs out of 365 interrogated. We have identified significant cis- (10%) and trans- (11%) eQTLs. Furthermore, we detected one genomic locus (rs1522653) that influences the expression levels of five miRNAs, thus unraveling a novel mechanism for co-regulation of miRNA expression. Primary fibroblasts were derived from the umbilical cord of 180 newborns of Western European origin recruited for the GenCord project. Mature miRNA expression phenotypes were generated using the micro-fluidics-based TaqMan® Human MiRNA Array v1.0 (Applied Biosystems). For each sample, expression levels for 365 known human mature miRNAs were assayed .

微小RNA（MicroRNAs, miRNAs）是一类调控性非编码RNA，可通过转录后调控影响人类相当一部分mRNA的生成。miRNA表达水平的个体间差异可能会调控其靶基因的表达，进而参与人类表型差异的形成，包括常见疾病的易感性。目前学界对miRNA水平受遗传调控的程度仍知之甚少。本研究针对GenCord项目中180名欧洲新生儿的原代成纤维细胞，检测了其中miRNA的表达水平，并通过关联分析筛选表达数量性状位点（eQTLs, expression quantitative traits loci）。本研究在365个被检测的miRNA中，成功检测到121个miRNA的稳定表达，并鉴定出占比10%的显著顺式eQTLs与占比11%的显著反式eQTLs。此外，本研究还发现一个基因组位点（rs1522653）可调控5个miRNA的表达，从而揭示了一种全新的miRNA表达共调控机制。本研究涉及的原代成纤维细胞均取自GenCord项目招募的180名西欧血统新生儿的脐带组织。成熟miRNA的表达表型通过基于微流控技术的TaqMan®人类miRNA芯片v1.0（应用生物系统公司，Applied Biosystems）完成检测与获取。所有样本均针对365种已知的人类成熟miRNA的表达水平进行了检测。