RT Journal Article
SR Electronic
T1 Exploring functional variation affecting ceRNA regulation in humans
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 016865
DO 10.1101/016865
A1 Mulin Jun Li
A1 Jiexing Wu
A1 Peng Jiang
A1 Wei Li
A1 Yun Zhu
A1 Daniel Fernandez
A1 Russell J. H. Ryan
A1 Yiwen Chen
A1 Junwen Wang
A1 Jun S. Liu
A1 X. Shirley Liu
YR 2015
UL http://biorxiv.org/content/early/2015/03/22/016865.abstract
AB MicroRNA (miRNA) sponges have been shown to function as competing endogenous RNAs (ceRNAs) to regulate the expression of other miRNA targets in the network by sequestering available miRNAs. As the first systematic investigation of the genome-wide genetic effect on ceRNA regulation, we applied multivariate response regression and identified widespread genetic variations that are associated with ceRNA competition using 462 Geuvadis RNA-seq data in multiple human populations. We showed that SNPs in gene 3’UTRs at the miRNA seed binding regions can simultaneously regulate gene expression changes in both cis and trans by the ceRNA mechanism. We termed these loci as endogenous miRNA sponge expression quantitative trait loci or “emsQTLs”, and found that a large number of them were unexplored in conventional eQTL mapping. We identified many emsQTLs are undergoing recent positive selection in different human populations. Using GWAS results, we found that emsQTLs are significantly enriched in traits/diseases associated loci. Functional prediction and prioritization extend our understanding on causality of emsQTL allele in disease pathways. We illustrated that emsQTL can synchronously regulate the expression of tumor suppressor and oncogene through ceRNA competition in angiogenesis. Together these results provide a distinct catalog and characterization of functional noncoding regulatory variants that control ceRNA crosstalk.