Non-inhibited miRNAs shape the cellular response to anti-miR.

ABSTRACT: Identification of primary microRNA (miRNA) gene targets is critical for developing miRNA-based therapeutics and understanding their mechanisms of action. However, disentangling primary target derepression induced by miRNA inhibition from secondary effects on the transcriptome remains a technical challenge. Here, we utilized RNA immunoprecipitation (RIP) combined with competitive binding assays to identify novel primary targets of miR-122. These transcripts physically dissociate from AGO2-miRNA complexes when anti-miR is spiked into liver lysates. mRNA target displacement strongly correlated with expression changes in these genes following in vivo anti-miR dosing, suggesting that derepression of these targets directly reflects changes in AGO2 target occupancy. Importantly, using a metric ba

SUBMITTER: Androsavich JR 

PROVIDER: S-EPMC4066772 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature