Knockdown of RNA editing proteins reshapes the HepaRG transcriptome and pharmacogene expression

Both proteins have been shown to have essential functions in the liver, including regulating the expression of drug-metabolizing enzymes. Here, using RNA-Seq, we profiled widespread changes to the hepatic transcriptome after knockdown (KD) of either ADAR or ADARB1 in HepaRG cells.

Nearly a thousand pharmacogenes had altered expression or alternative splicing across both KDs, with splice isoform switches occurring for both HNF4A and CYP2C9. The two ADAR proteins largely affected different sets of genes, with KD of ADAR having more widespread effects than KD of ADARB1. Subsequent analyses of differential editing indicated that most transcriptomic alterations were independent of RNA editing.