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Developmental and age-related changes in apolipoprotein B mRNA editing in mice
K Higuchi1, K Kitagawa, K Kogishi
1Department of Senescence Biology, Kyoto University, Japan.
Abstract:
Apolipoprotein B (apoB) mRNA is modified by a post-transcriptional editing reaction (C to U) changing a glutamine (CAA) to a translational stop codon (UAA) and producing apoB-48 mRNA in mammalian liver and intestine. Developmental and age-related changes in apoB mRNA editing were studied using two mouse strains with different aging processes (SAM-R/1 with a normal aging process and SAM-P/1 with an accelerated aging process). During growth of both strains, the proportion of unedited (apoB-100) mRNA decreased from 80% in the fetal liver at the 17th day of gestation to 30% in the liver of mature 2-month-old mice. Age-associated increase in the proportion of hepatic apoB-100 mRNA was observed from the age of 18 months in the SAM-R/1 strain. In the SAM-P/1 strain, apoB-100 mRNA in the liver continued to increase from the age of 10 months to death. The profiles of developmental and age-related changes in the proportion of two serum apoB isoproteins (apoB-100 and apoB-48) followed the extent of hepatic apoB mRNA editing. Age-related changes in the extent of apoB mRNA editing in the small intestine were not observed in either strain. A slight expression of apoB was detected by reverse transcriptase-polymerase chain reaction in the kidney, stomach, and colon, and age-associated change in the extent of editing was observed in the kidney. These correlated changes in apoB mRNA editing and serum apoB proteins suggest that RNA editing may be one mechanism involved in the regulation of lipoprotein biogenesis in biological development and in senescent mice. An age-associated decrease in the extent of hepatic apoB mRNA editing and increases of the proportion of serum apoB-100 protein were observed in senescent mice.
Insights
Apolipoprotein B (apoB) mRNA editing decreases with age in mouse liver, impacting serum protein levels. This RNA editing process is crucial for lipoprotein biogenesis, especially in aging mammals.
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- Apolipoprotein B (apoB) mRNA undergoes post-transcriptional editing (C to U), converting glutamine to a stop codon and producing apoB-48.
- This editing occurs in mammalian liver and intestine, influencing apoB protein isoforms.
Purpose of the Study:
- To investigate developmental and age-related changes in apoB mRNA editing.
- To compare editing patterns in mouse strains with normal (SAM-R/1) and accelerated (SAM-P/1) aging.
Main Methods:
- Studied apoB mRNA editing in liver and small intestine of two mouse strains during development and aging.
- Analyzed serum apoB-100 and apoB-48 protein levels.
- Utilized reverse transcriptase-polymerase chain reaction (RT-PCR) to detect apoB expression in other tissues.
Main Results:
- Hepatic apoB mRNA editing decreased during development (80% to 30%) in both strains.
- Age-associated increases in unedited apoB-100 mRNA were observed in the liver of older mice (from 18 months in SAM-R/1, from 10 months in SAM-P/1).
- Serum apoB protein profiles mirrored hepatic mRNA editing changes; no significant age-related changes were found in the small intestine.
Conclusions:
- Hepatic apoB mRNA editing decreases with age, particularly in senescent mice.
- Age-related changes in apoB mRNA editing correlate with alterations in serum apoB protein levels.
- RNA editing is a potential regulatory mechanism for lipoprotein biogenesis during development and aging.
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