RNA‐Seq identifies novel alternative transcripts of cytochrome P450s in human hepatocytes

Abstract

Most human genes can produce alternative transcripts by transcriptional regulation or RNA processing, which in many cases encode functionally distinct proteins. The cytochrome P450 enzymes (P450s) catalyze the oxidation of lipids, steroid hormones, drugs, and toxic chemicals. The purpose of this study was to identify novel transcripts of P450 genes and characterize their expression and induction in human hepatocytes. RNA sequencing (RNA‐Seq) was used to identify novel transcripts of P450s in human hepatocytes or HepaRG cells after treatment with rifampicin or phenobarbital. In 30 P450 genes with the expression levels >10 (FPKM: fragments per kilobase of exon per million fragments mapped) in human hepatocytes or HepaRG cells, RNA‐Seq identified 67 alternative transcription events, including exon skipping, intron retention, alternative splicing, and polyadenylation. Some events were reported in literature, but most were novel. Several novel events were confirmed by PCR or rapid amplification of cDNA ends plus DNA sequencing. Furthermore, differential expression of alternative transcripts was observed in some P450 genes after drug treatment.ConclusionRNA‐Seq identified novel transcripts for P450 genes. Alternative transcription variants of P450 genes had differential expression during drug treatments, which may serve as a potential mechanism for the differential enzyme activity in human liver.