Ontogenetic regulation of apolipoprotein B mRNA editing during human and rat development in vivo.
The solubilization and delivery of lipids in plasma rely on both forms of apolipoprotein B (apo B): apo B-100 and apo B-48. Apo B-48 is the translational product of apo B-100 mRNA that undergoes peritranscriptional conversion of C----U, replacing codon CAA (glutamine 2,153) with the inframe stop codon (UAA). We examined mRNA editing activity in the human and the rat by reverse transcription-polymerase chain reaction primer-extension analysis of intestine and liver total RNA. In rat intestine the percentage of apo B transcripts that undergo editing increases dramatically the day before birth (from approximately 1% to 80%), whereas the rat liver acquires an adult level of editing activity during the third postnatal week (rising from approximately 8% to 30%), when weaning is completed, bile acid composition matures, and plasma thyroid hormone levels peak. In contrast to the rat, the human intestine acquires adult levels of apo B mRNA editing relatively early in fetal development, rising from 10% at 10 weeks to approximately 80% by the end of the second trimester. Our results establish that apo B mRNA editing is 1) developmentally regulated in a tissue- and species-specific manner; 2) fully developed prenatally in both human and rat intestine, suggesting a crucial role of apo B-48 in mammalian fetal adaptation to extrauterine life; and 3) acquired early in human fetal intestine, implying a potential role for apo B-48 in prenatal lipid metabolism.
Patterson
A P
AP
Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
Tennyson
G E
GE
Hoeg
J M
JM
Sviridov
D D
DD
Brewer
H B
HB
D000818:Animals; D000831:Animals, Newborn; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000235:genetics*; D001483:Base Sequence; D005786:Gene Expression Regulation; D006801:Humans; D007223:Infant; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000196:embryology / Q000254:growth & development*; D008099:Liver / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014158:Transcription, Genetic
D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D012333:RNA, Messenger