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Isolation, characterization and developmental regulation of the human apobec-1 complementation factor (ACF) gene
J O Henderson1, V Blanc, N O Davidson
1Department of Internal Medicine, Washington University School of Medicine, 660 S. Euclid Ave, Box 8124, St. Louis, MO 63110, USA.
Biochimica Et Biophysica Acta
|November 24, 2001
Summary
Human apolipoprotein B mRNA editing is regulated by apobec-1 complementation factor (ACF). ACF mRNA shows complex splicing but constant levels during development, suggesting other factors control apo B mRNA editing increases.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Apolipoprotein B (apo B) mRNA undergoes essential C to U deamination in mammals.
- This editing is mediated by apobec-1 complementation factor (ACF) and apobec-1.
Purpose of the Study:
- To isolate and characterize the human ACF gene.
- To examine the tissue-specific and developmental expression of ACF.
- To investigate the role of ACF mRNA in regulating apo B mRNA editing.
Main Methods:
- Gene isolation and characterization.
- Analysis of alternative splicing and transcript variants.
- Examination of ACF mRNA abundance and expression patterns in fetal and adult tissues and cell lines.
Main Results:
- The human ACF gene spans ~80 kb with 15 exons, generating at least nine transcripts via alternative splicing.
- The majority of ACF transcripts (75-89%) encode functional protein.
- ACF mRNA splicing and abundance remained relatively constant during human intestinal and hepatic development.
Conclusions:
- ACF mRNA exhibits complex, differential, and tissue-specific splicing patterns.
- Despite complex splicing, ACF mRNA levels do not correlate with the developmental increase in intestinal apo B mRNA editing.
- Other regulatory mechanisms likely account for the developmental regulation of apo B mRNA editing in the human intestine.