The Human Cytochrome P450 1A1 mRNA Is Rapidly Degraded In HepG2 Cells

Abstract

The cytochromes P450 are a superfamily of enzymes that can carry out a wide range of oxidative reactions. While the transcriptional control of the cytochrome P450 genes has been relatively well-studied, posttranscriptional regulatory mechanisms that contribute to the regulation of P450s are much less well understood. We followed the decay of CYP1A1, CYP1A2, and CYP1B1 mRNAs after induction by the AH receptor ligand 2,3,7,8,-tetrachlorodibenzo-p-dioxin. CYP1A2 and CYP1B1 mRNAs were long-lived in this cell line (t12 > 24 h). In contrast, the CYP1A1 mRNA decays remarkably quickly. To determine if this rapid decay was unique to CYP1A1, we assessed the decay of selected human P450 and liver-specific mRNAs in HepG2 cells as a comparison. We analyzed albumin, phosphofructokinase, and GAPDH mRNAs and found that they were long-lived, with half-lives >24 h. We show that CYP2E1 mRNA can be detected in HepG2 cells by RT-PCR and that this mRNA also has a basal half-life of >24 h. Thus the CYP1A1 mRNA with its half-life of 2.4 h was one of the shortest-lived mRNA studied and is the most unstable of the cytochrome P450 mRNAs we have tested. The rapid decay of CYP1A1 mRNA is associated with a rapid loss in poly(A) tail length, suggesting that deadenylation is the first step in the decay pathway. The short half-life appears to be conserved across species, which suggests that this characteristic of the CYP1A1 mRNA is important for its function.