Molecular cloning of a human small intestinal apolipoprotein B mRNA editing protein.
Mammalian small intestinal apolipoprotein B (apo B) mRNA undergoes posttranscriptional cytidine deamination with the production of an in frame 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 extracts. The cDNA specifies a 236 residue protein which is 69% identical to the apo B mRNA editing protein (REPR) cloned from rat small intestine [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 contain the carboxyl-terminus leucine zipper motif identified in REPR but contains consensus phosphorylation sites as well as the conserved histidine and both cysteine residues identified as a Zn2+ binding motif in other cytidine deaminases. The distribution of HEPR mRNA was predominantly confined to the adult small intestine with lower levels detectable by reverse-transcription polymerase chain reaction amplification in the stomach, colon and testis. These differences in the structure and distribution of the human as compared to the rat apo B mRNA editing protein suggest an important evolutionary adaptation in the mechanisms restricting apo B48 production to the small intestine.
Hadjiagapiou
C
C
Department of Medicine, University of Chicago, IL 60637.
Giannoni
F
F
Funahashi
T
T
Skarosi
S F
SF
Davidson
N O
NO
D000071479:APOBEC-1 Deaminase; D000595:Amino Acid Sequence; D000818:Animals; D001055:Apolipoproteins B / Q000235:genetics*; D001483:Base Sequence; D003001:Cloning, Molecular; D003564:Cytidine Deaminase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D018076:DNA, Complementary; D005333:Fetus / Q000737:chemistry; D006801:Humans; D007583:Jejunum / Q000737:chemistry* / Q000378:metabolism; D016350:Leucine Zippers; D008969:Molecular Sequence Data; D012323:RNA Processing, Post-Transcriptional / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D013698:Templates, Genetic; D014018:Tissue Distribution; D014158:Transcription, Genetic; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D001055:Apolipoproteins B; D018076:DNA, Complementary; D012333:RNA, Messenger; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D000071479:APOBEC-1 Deaminase; C000605089:APOBEC1 protein, human; C000605091:Apobec1 protein, rat; D003564:Cytidine Deaminase