Identification of an alternative 5' untranslated region of the adenomatous polyposis coli gene.

cDNA clones, representing transcripts expressed in human fetal brain, have been isolated that specify the 5' end of the adenomatous polyposis coli (APC) gene. Sequence analyses have revealed an alternative 5' untranslated region (5'UTR) of the APC gene; this region is comprised of at least 103 basepairs. A comparison of this alternative UTR with the published sequence of the APC-gene indicates that these two 5'UTR sequences diverge beyond nucleotide position -20 with respect to the A of the authentic translational initiation codon. These data suggest that two APC-specific promoter elements exist, giving rise to two different untranslated regions. Within the alternative UTR, we have identified 3 additional AUG codons, located 5' to the intrinsic APC initiation site. Two of these AUG codons are located in a nucleotide context that favours initiation of truncated translation products. The relevance of these additional AUG codons to a regulatory mechanism acting at the post-transcriptional level of APC gene expression is discussed.