Adenosine-to-Inosine RNA Editing and N6-Methyladenosine Modification Modulating Expression of Drug Metabolizing Enzymes

Abstract

Interindividual differences in the expression and activity of drug metabolizing enzymes including cytochrome P450, UDP-glucuronosyltransferase, and esterases cause variable therapeutic efficacy or adverse events of drugs. As the major mechanisms causing the variability in the expression of drug metabolizing enzymes, transcriptional regulation by transcription factors, epigenetic regulation including DNA methylation, and posttranscriptional regulation by microRNA are well known. Recently, adenosine-to-inosine RNA editing and methylation of adenosine at the N6 position on RNA have emerged as novel regulators of drug metabolism potency. In this review article, the current knowledge of these two prevalent types of posttranscriptional modification mediated modulation of drug metabolism involved genes is introduced. SIGNIFICANCE STATEMENT Elucidation of the significance of adenosine-to-inosine RNA editing and N6-methyladenosine in the regulation of drug metabolizing enzymes is expected to lead to a deeper understanding of interindividual variability in the therapeutic efficacy or adverse effects of medicines.