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Identification of cis - and trans -regulatory variation modulating microRNA expression levels in human fibroblasts

2010; Cold Spring Harbor Laboratory Press; Volume: 21; Issue: 1 Linguagem: Inglês

10.1101/gr.109371.110

1549-5469

Christelle Borel, Samuel Deutsch, Audrey Letourneau, Eugenia Migliavacca, Stephen B. Montgomery, Antigone S. Dimas, Charles E. Vejnar, Homa Attar, Maryline Gagnebin, Corinne Gehrig, Emilie Falconnet, Yann Dupré, Emmanouil T. Dermitzakis, Stylianos E. Antonarakis,

RNA modifications and cancer

MicroRNAs (miRNAs) are regulatory noncoding RNAs that affect the production of a significant fraction of human mRNAs via post-transcriptional regulation. Interindividual variation of the 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 coregulation of miRNA expression.