The expression of apoB mRNA editing factors is not the sole determinant for the induction of editing in differentiating Caco-2 cells.
Apolipoprotein B mRNA is edited at cytidine 6666 in the enterocytes lining the small intestine of all mammals; converting a CAA codon to a UAA stop codon. The conversion is approximately 80% efficient in this tissue and leads to the expression of the truncated protein, ApoB48, essential for secretion of dietary lipid as chylomicrons. Caco-2 cell raft cultures have been used as an in vitro model for the induction of editing activity during human small intestinal cell differentiation. This induction of apoB mRNA editing has been ascribed to the expression of APOBEC-1. In agreement our data demonstrated differentiation-dependent induction of expression of the editing enzyme APOBEC-1 and in addition we show alternative splicing of the essential auxiliary factor ACF. However, transfection of these editing factors in undifferentiated proliferating Caco-2 cells was not sufficient to induce robust apoB mRNA editing activity. Only differentiation of Caco-2 cells could induce more physiological like levels of apoB mRNA editing. The data suggested that additional regulatory mechanism(s) were induced by differentiation that controlled the functional activity of editing factors.
Galloway
Chad A
CA
Department of Biochemistry and Biophysics, University of Rochester School of Medicine, 601 Elmwood Ave, Rochester, NY 14642, USA.
Smith
Harold C
HC
D000071479:APOBEC-1 Deaminase; D017398:Alternative Splicing; D053283:Apolipoprotein B-48 / Q000096:biosynthesis / Q000235:genetics; D001055:Apolipoproteins B / Q000235:genetics; D018938:Caco-2 Cells; D002454:Cell Differentiation / Q000235:genetics*; D003564:Cytidine Deaminase / Q000235:genetics*; D020895:Enterocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007421:Intestine, Small / Q000166:cytology* / Q000201:enzymology; D017393:RNA Editing / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*
C411647:A1CF protein, human; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D016601:RNA-Binding Proteins; D000071479:APOBEC-1 Deaminase; C000605089:APOBEC1 protein, human; D003564:Cytidine Deaminase