The p27 catalytic subunit of the apolipoprotein B mRNA editing enzyme is a cytidine deaminase.
The messenger RNA for apolipoprotein B undergoes a discrete and specific C to U editing of nucleotide 6666. This generates a stop translation 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 do not have intrinsic editing activity, has recently been identified and 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 zinc coordinating region of the active site to cytidine deaminases from Escherichia coli, Bacillus subtilis, yeast, and man and to deoxycytidylate 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. The homologous E. coli cytidine deaminase does not confer editing activity. The zinc-specific chelating agent o-phenanthroline abolishes p27 activity and site-specific apolipoprotein B mRNA editing in rat enterocyte editing extracts. We conclude that p27 is the catalytic subunit of the apolipoprotein B mRNA editing enzyme and is a zinc-containing cytidine deaminase.
Navaratnam
N
N
Medical Research Council Molecular Medicine Group, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
Morrison
J R
JR
Bhattacharya
S
S
Patel
D
D
Funahashi
T
T
Giannoni
F
F
Teng
B B
BB
Davidson
N O
NO
Scott
J
J
D000071479:APOBEC-1 Deaminase; D000595:Amino Acid Sequence; D000818:Animals; D001055:Apolipoproteins B / Q000235:genetics*; D002614:Chelating Agents / Q000494:pharmacology; D002645:Chickens; D003564:Cytidine Deaminase / Q000378:metabolism*; D007422:Intestines / Q000201:enzymology; D008969:Molecular Sequence Data; D010446:Peptide Fragments; D017393:RNA Editing / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017386:Sequence Homology, Amino Acid; D014981:Xenopus; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D001055:Apolipoproteins B; D002614:Chelating Agents; D010446:Peptide Fragments; D012333:RNA, Messenger; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D000071479:APOBEC-1 Deaminase; C000605091:Apobec1 protein, rat; D003564:Cytidine Deaminase