Role of the defective splicing of mRNA in the lack of pulmonary expression of constitutively active receptor in rat

The mammalian constitutively active receptor (CAR) is a ligand-activated transcription factor that participates in controlling the expression of cytochrome P450 2B (CYP2B) genes in response to xenobiotics; in an organ-specific manner. In the presence of phenobarbital (PB) or PB-type agents, hepatic CYP2B forms are highly inducible. In contrast, PB-dependent increases in the expression of CYP2B activities are rarely observed in the lung. Mature CAR mRNA could be detected in the liver of 7-week-old Wistar rats by RTPCR, while lung CAR mRNA had a 91 bp extra nucleotide sequence inserted in a coding region of hepatic CAR mRNA. By comparing the full-length sequence of hepatic CAR mRNA, including 5'- and 3'-untranslated region (3'-UTR), with the genomic sequence completed in the present study, the genomic structure was clarified to consist of 9 exons and 8 introns, in which the coding region expanded from exon 2 in close to its 5'-end to the first one-third of exon 9 after 159 bp of 5'-UTR in the most frequently obtained cDNA clones. In pulmonary CAR mRNA, intron 6 was not spliced out, implying that the lack of CAR in the lung might in part result from the incomplete splicing of precursor mRNA during its maturation.