The human cytochrome P450 1A1 mRNA is rapidly degraded in HepG2 cells

The cytochromes P450 are a superfamily of enzymes that can carry out a wide range of oxidative reactions. While the transcriptional control of the cyt ochrome P450 genes has been relatively well-studied, posttranscriptional re gulatory mechanisms that contribute to the regulation of P450s are much les s well understood. We followed the decay of CYP1A1, CYP1A2, and CYP1B1 mRNA s after induction by the AH receptor ligand 2,3,7,8,-tetrachlorodibenzo-p-d ioxin, CYP1A2 and CYP1B1 mRNAs were long-lived in this cell line (t(1/2) > 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 selecte d human P450 and liver-specific mRNAs in HepG2 cells as a comparison. We an alyzed albumin, phosphofructokinase, and GAPDH mRNAs and found that they we re long-lived, with half-lives >24 h, We show that CYP2E1 mRNA can be detec ted 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 s hortest-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 r apid loss in poly(A) tail length, suggesting that deadenylation is the firs t step in the decay pathway. The short half-life appears to be conserved ac ross species, which suggests that this characteristic of the CYP1A1 mRNA is important for its function. (C) 2000 Academic Press.