Genetic control of primary microRNA insight into cis- and trans-regulatory variations by RNA-seq

To search for genetic regulators influencing miRNA transcript abundance, we performed a genome-wide association study (GWAS) to identify quantitative trait loci associated with primary miRNA transcript abundance (pri-miQTL) using genotype data from HapMap CEU phased data. We detected robust expression for 150 pri-miRNAs out of 1523 interrogated using RNA-seq. We have identified some pri-miRNAs that showed significant evidence for cis- (34%) and trans-pri-miQTLs (3%). Furthermore, we observed that multiple cis-pri-miQTLs, showed allele-specific expression associated with single pri-miRNA expression. Interestingly, a cis-regulatory variation influenced the expression levels of two pri-miRNAs that expressed identical mature sequences. We also observed that a single trans-regulatory variation was associated with multiple unrelated pri-miRNAs: rs292253 was associated with the expression of hsa-mir-3181, hsa-mir-3665 and hsa-mir-762. These findings revealed that the expression of pri-miRNA detected by RNA-seq can be used to identify pri-miQTLs, as an alternative method to dissect the genetic control mechanisms governing pri-miRNA expression.