Apolipoprotein B mRNA editing in 12 different mammalian species: hepatic expression is reflected in low concentrations of apoB-containing plasma lipoproteins.
Abstract: Two different isoproteins are encoded by the apolipoprotein (apo) B gene, apoB-48 and apoB-100. ApoB-48, core component of intestinally derived chylomicrons, has an accelerated plasma turnover as compared with the full-length protein apoB-100. A posttranscriptional modification of the apoB mRNA by conversion of cytidine into uridine at nucleotide position 6666 changes the genomically encoded glutamine codon CAA at amino acid residue 2153 into a translational stop codon UAA. This mRNA editing explains the formation of the truncated isoform apoB-48. In the present investigation editing of apoB mRNA in liver and intestine from 12 different mammalian species was measured by a quantitative primer extension analysis of reverse-transcribed and polymerase chain reaction- (PCR) amplified apoB mRNA in order to determine whether i) editing of apoB mRNA is generally restricted to the intestine or may also be found in the liver of other species than rodents, and ii) hepatic expression of apoB mRNA editing influences lipoprotein concentrations in plasma. Intestinal apoB mRNA was edited at high levels in all species, 40% in sheep, 73% in horse, 82% in pig, 84% in dog, 84% in cat, 87% in guinea pig, 88% in rat, 89% in mouse, and > 90% in human, monkey, cow, and rabbit. In liver apoB mRNA was edited to 18% in dog, to 43% in horse, to 62% in rat, and to 70% in mouse. Low levels of editing below 1% were detected in liver of rabbit and guinea pig. In contrast, hepatic apoB mRNA from human, monkey, pig, cow, sheep, and cat liver was not edited. The results of the primer extension analysis were confirmed by cloning and sequencing of the PCR products from dog, horse, cat, guinea pig, sheep, and cow for all of which the apoB cDNA sequence had not been established by previous investigations. Primer extension analysis of apoB mRNA from dog intestine and dog liver indicated C/U editing at C6655 in addition to C6666. Cloning and sequencing of apoB cDNA from dog liver and intestine confirmed additional C/U editing at C6655 which changes ACA for threonine at amino acid residue 2149 into AUA for isoleucine. Synthesis and secretion of apoB-48-containing lipoproteins from liver was demonstrated by pulse labeling of freshly isolated horse hepatocytes and immunoprecipitation with apoB-specific antibodies or density gradient ultracentrifugation. The concentrations of VLDL, LDL, and HDL in all species were determined after fractionation by density gradient ultracentrifugation.(ABSTRACT TRUNCATED AT 400 WORDS)
Publication Date: 1993-08-01 PubMed ID: 8409768
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research study investigates the mRNA editing of apolipoprotein B in the liver and intestine of 12 different mammalian species to understand its influence on plasma lipoprotein concentrations. The findings suggest that the process occurs predominantly in the intestines across all species and at varied levels in the liver.
Introduction to Apolipoprotein B and its Isoproteins
- The apolipoprotein (apo) B gene encodes two different isoproteins: apoB-48 and apoB-100.
- These two isoproteins play a significant role in the body’s lipid metabolism. The apoB-48 acts as the core component of intestinally derived chylomicrons, while the full-length protein apoB-100 is involved with a slower plasma turnover.
Process of mRNA Editing
- The body performs a posttranscriptional modification of the apoB mRNA, which involves the conversion of the cytidine molecule into uridine at nucleotide position 6666.
- This action changes the genomically encoded glutamine codon CAA at amino acid residue 2153 into a translational stop codon UAA.
- This mRNA editing results in the creation of the truncated isoform apoB-48.
Main Objectives of the Study
- The researchers sought to determine whether the editing of apoB mRNA takes place only in the intestine or could also be found in the livers of species other than rodents.
- Secondly, the study intended to explore if the hepatic expression of apoB mRNA editing had any effects on lipoprotein concentrations in plasma.
Pivotal Findings of the Study
- Upon investigation, high level of intestinal apoB mRNA editing was observed across the board in all the surveyed species.
- Editing of apoB mRNA in liver varied across the species assessed. It was found to be high in some like the rat and mouse, moderate in others like the dog and horse, and almost negligible in the rabbit and guinea pig.
- Interestingly, apoB mRNA from the liver of certain species like humans, monkeys, pigs, cows, sheep, and cats showed no signs of editing.
Additional Discoveries
- In addition to the core findings, additional C/U editing at C6655 was discovered in the liver and intestines of dogs.
- Synthesis and secretion of apoB-48-containing lipoproteins from the liver were also noted during the study.
Implications of the Study
- This research implies a potential link between mRNA editing of apoB, the formation of certain lipoproteins, and their concentrations in plasma.
- The findings also suggest a species-specific variability in the occurrence of apoB mRNA editing in liver cells.
- Understanding these processes can provide valuable insights into lipid metabolism and its regulation across various mammalian species.
Cite This Article
APA
Greeve J, Altkemper I, Dieterich JH, Greten H, Windler E.
(1993).
Apolipoprotein B mRNA editing in 12 different mammalian species: hepatic expression is reflected in low concentrations of apoB-containing plasma lipoproteins.
J Lipid Res, 34(8), 1367-1383.
Publication
Researcher Affiliations
- Medizinische Kernklinik und Poliklinik, Universitäts-Krankenhaus Eppendorf, Hamburg, Germany.
MeSH Terms
- Adult
- Animals
- Apolipoproteins B / genetics
- Apolipoproteins B / metabolism
- Base Sequence
- Cats
- Cattle
- DNA, Complementary / chemistry
- Dogs
- Guinea Pigs
- Horses
- Humans
- Intestinal Mucosa / metabolism
- Lipoproteins / blood
- Liver / metabolism
- Macaca mulatta
- Mice
- Middle Aged
- Molecular Sequence Data
- RNA Editing
- RNA, Messenger / metabolism
- Rabbits
- Rats
- Sheep
- Species Specificity
- Swine
Citations
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