THE P27 CATALYTIC SUBUNIT OF THE APOLIPOPROTEIN-B MESSENGER-RNA EDITING ENZYME IS A CYTIDINE DEAMINASE

The messenger RNA for apolipoprotein B undergoes a discrete and specif ic C to U editing of nucleotide 6666. This generates a stop translatio n codon and defines the carboxyl terminus of apolipoprotein B48. A 27- kDa rat intestinal protein that does not itself edit apolipoprotein B mRNA, but confers editing activity on chick intestinal extracts that d o not have intrinsic editing activity, has recently been identified an d its cDNA cloned (Teng, B., Burant, C. F., and Davidson, N. O. (1993) Science 260, 1816-1819). Here we show that p27 is homologous in the z inc coordinating region of the active site to cytidine deaminases from Escherichia coli, Bacillus subtilis, yeast, and man and to deoxycytid ylate deaminases from T2 and T4 bacteriophages and man. p27 expressed in Xenopus laevis oocyte extracts has cytidine deaminase activity and specifically confers editing activity on chick intestinal extracts. Th e homologous E. coli cytidine deaminase does not confer editing activi ty. The zinc-specific chelating agent o-phenanthroline abolishes p27 a ctivity and site-specific apolipoprotein B mRNA editing in rat enteroc yte editing extracts. We conclude that p27 is the catalytic subunit of the apolipoprotein B mRNA editing enzyme and is a zinc-containing cyt idine deaminase.