Characterization of the human apobec-1 gene: Expression in gastrointestinal tissues determined by alternative splicing with production of a novel truncated peptide

Ken Ichi Hirano, Jing Min, Toru Funahashi, David A. Baunoch, Nicholas O. Davidson

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

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 that changes He80 to Met. 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 ~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.

Original languageEnglish
Pages (from-to)847-859
Number of pages13
JournalJournal of lipid research
Volume38
Issue number5
StatePublished - May 1997

Keywords

  • Apolipoprotein B mRNA
  • Developmental regulation
  • Gene structure
  • Intestinal peptide
  • RNA editing

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