Structural analysis of the gene encoding rat uricase.

The uricase gene was isolated from rat genomic DNA libraries. The gene spans 40 kb and consists of eight exons. All the exon-intron junctional sequences conform to the canonical GT/AG rule. The restriction map of the isolated clones and Southern blot analysis revealed that the enzyme is encoded by a single-copy gene. Analysis of the transcription initiation site of rat uricase mRNA indicated the differential use of consecutive nucleotides; the principal repeat is located 55 nucleotides upstream from the first methionine codon. Nucleotide sequence analysis of the 5'-flanking region showed the presence of a TATA (ATAAAA) sequence at nucleotides 30 to 25 and of a CAAT (GGTCAAT) sequence at nucleotides 63 to 57 upstream of the principal transcription initiation site. The 5'-flanking region contains another possible regulatory sequence (TGTCGACA) homologous to the cAMP-regulatory element. The palindromic sequence is located 158 to 151 nucleotides upstream from the transcription initiation site, surrounded by a direct repeat (TCAGCAA).