Mapping the miRNA-mRNA Interactome in Human Hepatocytes and Identification of Functional mirSNPs in Pharmacogenes.

ABSTRACT: MiRNAs regulate the expression of hepatic genes involved in pharmacokinetics and pharmacodynamics. Genetic variants affecting miRNA binding (mirSNPs) have been associated with altered drug response, but previously used methods to identify miRNA binding sites and functional mirSNPs in pharmacogenes are indirect and limited by low throughput. We utilized the high-throughput chimeric-eCLIP assay to directly map thousands of miRNA-mRNA interactions and define the miRNA binding sites in primary hepatocytes. We then used the high-throughput PASSPORT-seq assay to functionally test 262 potential mirSNPs with coordinates overlapping the identified miRNA binding sites. Using chimeric-eCLIP, we identified a network of 448 miRNAs that collectively target 11,263 unique genes in primary hepatocytes pool

SUBMITTER: Powell NR 

PROVIDER: S-EPMC9007393 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature