Alterations in mRNA stability during rat liver regeneration
Abstract
We examined the in vivo transcriptional and posttranscriptional regulation of various genes involved in hepatocyte growth and replication that exhibited changes in steady-state mRNA levels after 70% partial hepatectomy (PH). Of the 19 genes examined by nuclear run-on assay, 17 demonstrated no change in transcriptional activity through the first 96 h of regeneration. However, results from in vivo half-life determinations indicated that changes in mRNA stability played a critical role in regulating transcript levels during liver regeneration. For many of the genes, alterations in transcript abundance correlated with similar changes in mRNA half-lives. Inhibition of protein synthesis by cycloheximide was generally associated with increased levels of mRNA expression, but no detectable changes in transcriptional rates in both control and regenerating rat liver. Finally, genomic methylation status was investigated by Southern analysis for several genes that displayed changes in mRNA stability. Interestingly, increases in mRNA half-lives for the genes p53, c-myc, H-ras, and ornithine decarboxylase were associated with decreased genomic methylation. In conclusion, regulation of gene expression beyond the immediate early phase of te cell cycle during rat liver regeneration after PH occurs predominantly at the posttranscriptional level. mRNA stability appears to be a significant factor in this control, and may itself be modulated by the methylation status of the corresponding genomic DNA.
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Protein decay kinetics is a state-of-the-art tool favored over RNA kinetics for assessing RNA stability because it allows integrated recording of all relevant translational characteristics.
“Protein decay kinetics is regarded as a state-of-the-art tool favored over RNA kinetics because it allows integrated recording of all relevant translational characteristics in the function-oriented manner required for the objective of our investigations.20”
From Modification of antigen-encoding RNA increases stability, translational efficacy, and T-cell stimulatory capacity of dendritic cells (2006) · cites this paper as [19]
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Holtkamp, S., Kreiter, S., Selmi, A., Simon, P., Koslowski, M., Huber, C., Türeci, O., & Sahin, U. (2006) · Blood · doi:10.1182/blood-2006-04-015024 · Cited by 625 · see citing works
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Issa, J.-P. (2014) · Journal of Clinical Investigation · doi:10.1172/jci69735 · Cited by 419 · see citing works
- Authors
- Kren, B. T., Trembley, J. H., & Steer, C. J.
- Affiliations
- Department of Medicine, University of Minesota Medical School, Minneapolis 55455, USA.
- ORCID
- Trembley, J. H.
- Venue
- American Journal of Physiology-Gastrointestinal and Liver Physiology
- Publisher
- American Physiological Society
- Published
- 1996-05-01
- Volume
- 270
- Issue
- 5
- Pages
- G763-G777
- ISSN
- 0193-1857 (ISSN-L)
- 1522-1547
- OpenAlex
- W2204583878
- Cited by
- 49
- References
- 0
- Citations by year
- 2024: 1 · 2021: 1 · 2019: 1 · 2018: 1 · 2014: 2
- FWCI
- 2.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Gastrointestinal and Liver Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK044649)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Keywords
- liver regeneration, mRNA stability, post-transcriptional regulation, partial hepatectomy, mRNA half-life, genomic DNA methylation, p53, c-Myc, H-Ras, ornithine decarboxylase, hepatocyte proliferation, transcriptional regulation, cycloheximide
- MeSH terms
- Animals, Half-Life, Hepatectomy, Homeostasis, Liver Regeneration, Male, Ornithine Decarboxylase, Genes, ras, Receptors, Cell Surface, RNA, Messenger, Transcription, Genetic, Gene Expression, Genes, Tumor Suppressor, Genes, myc, Rats, Sprague-Dawley, Drug Resistance, Multiple, Cytochrome P-450 CYP2E1, Asialoglycoprotein Receptor, Rats
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