title: Characterization of the human apobec-1 gene: expression in gastrointestinal tissues determined by alternative splicing with production of a novel truncated peptide.
abstract: 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 understand the tissue-restricted pattern of apobec-1 expression, we have isolated 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 translated. 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 functionally silent, gene polymorphism was detected than changes Ilc80 to MCl. RNase protection and reverse-transcription PCR analysis demonstrated the presence of an exon 2-skipped form of apobec-1 mRNA that arises through use of an alternative splice acceptor. This alternative splicing causes a frame-shift that produces a novel, 36 amino acid peptide. The exon 2-skipped form accounts for approximately 50% of apobec-1 mRNA in the adult small intestine and up to 90% of apobec-1 mRNA in the developing gut. An antipeptide antibody identified the truncated protein in villus cells of the adult small intestine. These data suggest that exon 2-skipping may represent an important control mechanism regulating apobec-1 gene expression in humans.
authors.affiliation: Department of Medicine, University of Chicago, IL 60637, USA.
authors.forename: K
authors.initials: K
authors.lastname: Hirano
authors.forename: J
authors.initials: J
authors.lastname: Min
authors.forename: T
authors.initials: T
authors.lastname: Funahashi
authors.forename: D A
authors.initials: DA
authors.lastname: Baunoch
authors.forename: N O
authors.initials: NO
authors.lastname: Davidson
mesh_terms: D000071479:APOBEC-1 Deaminase; D000328:Adult; D017398:Alternative Splicing; D001055:Apolipoproteins B / Q000235:genetics*; D001483:Base Sequence; D003564:Cytidine Deaminase / Q000235:genetics*; D004064:Digestive System / Q000378:metabolism*; D015894:Genome, Human; D006801:Humans; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics*; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D001055:Apolipoproteins B; D012333:RNA, Messenger; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D000071479:APOBEC-1 Deaminase; C000605089:APOBEC1 protein, human; D003564:Cytidine Deaminase