TY - JOUR
T1 - Isolation, characterization and developmental regulation of the human apobec-1 complementation factor (ACF) gene
AU - Henderson, J. O.
AU - Blanc, V.
AU - Davidson, N. O.
N1 - Funding Information:
This work was supported by NIH grants HL-38180 and DK-56260 (NOD) and a NIH Digestive Disease Research Core Center (DDRCC) grant DK52574 (NOD).
PY - 2001/11/11
Y1 - 2001/11/11
N2 - Mammalian apolipoprotein B (apo B) mRNA undergoes site-specific C to U deamination which is mediated by a multicomponent enzyme complex containing a minimal core composed of apobec-1 and a complementation factor, ACF. We have isolated and characterized the human ACF gene and examined its tissue-specific and developmental expression. The ACF gene spans ∼ 80 kb and contains 15 exons, three of which are non-coding. Multiple alternative splice acceptor sites were found, generating at least nine different transcripts. Of these, the majority (∼ 75-89%) encode functional protein. In order to examine the role of ACF mRNA expression in the regulation of apo B mRNA editing, we examined a panel of fetal intestinal and hepatic mRNAs as well as RNA from an intestinal cell line. A developmental increase in C to U RNA editing has been previously noted in the human intestine. In both instances, the pattern of alternative splicing and overall abundance of ACF mRNA was relatively constant during development in both liver and small intestine. Taken together, the data demonstrate a complex pattern of differential, tissue-specific splicing of ACF mRNA, but suggest that other mechanisms are responsible for the developmental increase noted in intestinal apo B mRNA editing in humans.
AB - Mammalian apolipoprotein B (apo B) mRNA undergoes site-specific C to U deamination which is mediated by a multicomponent enzyme complex containing a minimal core composed of apobec-1 and a complementation factor, ACF. We have isolated and characterized the human ACF gene and examined its tissue-specific and developmental expression. The ACF gene spans ∼ 80 kb and contains 15 exons, three of which are non-coding. Multiple alternative splice acceptor sites were found, generating at least nine different transcripts. Of these, the majority (∼ 75-89%) encode functional protein. In order to examine the role of ACF mRNA expression in the regulation of apo B mRNA editing, we examined a panel of fetal intestinal and hepatic mRNAs as well as RNA from an intestinal cell line. A developmental increase in C to U RNA editing has been previously noted in the human intestine. In both instances, the pattern of alternative splicing and overall abundance of ACF mRNA was relatively constant during development in both liver and small intestine. Taken together, the data demonstrate a complex pattern of differential, tissue-specific splicing of ACF mRNA, but suggest that other mechanisms are responsible for the developmental increase noted in intestinal apo B mRNA editing in humans.
KW - Alternative splicing
KW - Apolipoprotein B
KW - Gene structure
KW - RNA editing
KW - RNA-binding protein
UR - http://www.scopus.com/inward/record.url?scp=0035846449&partnerID=8YFLogxK
U2 - 10.1016/S0167-4781(01)00295-0
DO - 10.1016/S0167-4781(01)00295-0
M3 - Article
C2 - 11718896
AN - SCOPUS:0035846449
SN - 0167-4781
VL - 1522
SP - 22
EP - 30
JO - Biochimica et Biophysica Acta - Gene Structure and Expression
JF - Biochimica et Biophysica Acta - Gene Structure and Expression
IS - 1
ER -