CHARACTERIZATION OF THE HUMAN APOBEC-1 GENE - EXPRESSION IN GASTROINTESTINAL TISSUES DETERMINED BY ALTERNATIVE SPLICING WITH PRODUCTION OF A NOVEL TRUNCATED PEPTIDE

In humans, both the expression of apobec-1 and the C to U deamination of apoB mRNA are confined to the small intestine. In order to understa nd the tissue-restricted pattern of apobec-1 expression, we have isola ted the chromosomal gene spanning the human apobec-1 locus. The human apobec-1 gene spans 18 kb and contains five exons, all of which are tr anslated. Transcription initiation, determined by RNase protection and primer extension analyses, is localized to a single start site 34 nt upstream of the open-reading frame in exon 1. A common, but functional ly silent, gene polymorphism was detected that changes Ile80 to Met. R Nase protection and reverse-transcription PCR analysis demonstrated th e presence of an exon 2-skipped form of apobec-1 mRNA that arises thro ugh use of an alternative splice acceptor. This alternative splicing c auses a frame-shift that produces a novel, 36 amino acid peptide. The exon 2-skipped form accounts for similar to 50% of apobec-1 mRNA in th e adult small intestine and up to 90% of apobec-1 mRNA in the developi ng gut. An antipeptide antibody identified the truncated protein in vi llus cells of the adult small intestine. These data suggest that exon 2-skipping may represent an important control mechanism regulating apo bec-1 gene expression in humans.