Alterations in mrna stability during rat liver regeneration.
Kren, Betsy T., Janeen H. Trembley, and Clifford J. Steer.
Departments of Medicine and Cell Biology, University of Minnesota
Medical School, Minneapolis, Minnesota 55455
APStracts 2:0222G, 1995.
We examined the in vivo transcriptional and posttranscriptional
regulation of various genes involved in hepatocyte growth and
replication which exhibited changes in steady-state mRNA levels
following 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 which 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 the 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.
Received 13 July 1995; accepted in final form 18 October 1995.
APS Manuscript Number G290-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95