MOLECULAR-CLONING OF A HUMAN SMALL-INTESTINAL APOLIPOPROTEIN-B MESSENGER-RNA EDITING PROTEIN

Mammalian small intestinal apolipoprotein B (ape B) mRNA undergoes pos ttranscriptional cytidine deamination with the production of an in fra me stop codon and the translation of apo B48. We have isolated a cDNA from human jejunum which mediates in vitro editing of a synthetic apo B RNA template upon complementation with chicken intestinal S100 extra cts. The cDNA specifies a 236 residue protein which is 69% identical t o the apo B mRNA editing protein (REPR) cloned from rat small intestin e [Teng, B., Burant, C. F. and Davidson, N.O. (1993) Science 260, 1816 -1819] and which, by analogy, is referred to as HEPR. HEPR does not co ntain the carboxyl-terminus leucine zipper motif identified in REPR bu t contains consensus phosphorylation sites as well as the conserved hi stidine and both cysteine residues identified as a Zn2+ binding motif in other cytidine deaminases. The distribution of HEPR mRNA was predom inantly confined to the adult small intestine with lower levels detect able by reverse-transcription polymerase chain reaction amplification in the stomach, colon and testis. These differences in the structure a nd distribution of the human as compared to the rat apo B mRNA editing protein suggest an important evolutionary adaptation in the mechanism s restricting apo B48 production to the small intestine.