Rat ornithine decarboxylase gene. Nucleotide sequence, potential regulatory elements, and comparison to the mouse...

Expression of ornithine decarboxylase is regulated by a variety of hormonal and other stimuli in rat cells and tissues. To study this phenomenon at the molecular level, we isolated and sequenced a cDNA-encoding rat ornithine decarboxylase and deduced its amino acid sequence. The cDNA clone was used to isolate a clone from a rat genomic library which contained the sequence of the entire rat ornithine decarboxylase gene. The gene comprised 12 exons and 11 introns and spanned 7.7 kilobases. Two polyadenylation signals (AATAAA) were located 310 and 697 base pairs 3' to the translational termination codon and were responsible for the occurrence of two hybridizing mRNA species in Northern blots of rat cells and tissues. S1 nuclease mapping suggested that there were multiple transcriptional start sites; the major one appeared to be located 2269 base pairs of genomic sequence 5' to the ATG translational initiation site, representing 274 bases of mRNA. Several potential regulatory elements were identified in the 5'-promoter regions or in the first intron: a TATA box, GC boxes, AP-1 and AP-2 binding sites, a cAMP-responsive element, a glucocorticoid regulatory element, and RNA polymerase III promoter sequences. The 5'-noncoding region of the mRNA was extremely rich in G + C; secondary structure predictions suggested that almost this entire region could form stable secondary structures, with an overall free energy of formation (delta G) of -114 kcal/mol. The potential regulatory elements identified in both the promoter region of the gene and the 5'-untranslated region of the mRNA may be involved in the complex regulation of rat ornithine decarboxylase expression.