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Erythropoietin mRNA levels are governed by both the rate of gene
transcription and posttranscriptional events
MA Goldberg, CC Gaut and HF Bunn
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
The human hepatoma cell line, Hep3B, synthesizes large quantities of
erythropoietin (Epo) mRNA and protein in a regulated manner in response to
hypoxia and cobaltous chloride (CoCl2). To further understand the
regulation of Epo gene expression, we studied the effects of hypoxia and
CoCl2 on the rate of Epo gene transcription. While Northern blot analyses
showed that steady-state Epo mRNA levels increase more than 50- fold in
response to hypoxia or CoCl2, nuclear run-off experiments demonstrated only
a 10-fold increase in Epo gene transcription in response to these stimuli.
In the presence of either actinomycin D (Act D) or cycloheximide, the
stability of biologically functional Epo mRNA was much greater than that
observed in the absence of these agents and much greater than that which
has been reported in vivo. These findings suggest that the stability of Epo
mRNA is modulated by the transcription and translation of rapidly turning
over gene product(s). Thus, Epo mRNA levels are determined by both the rate
of gene transcription and posttranscriptional events. These experiments
demonstrate a potential pitfall in estimating mRNA half-lives based on Act
D chase experiments alone.
Volume 77,
Issue 2,
pp. 271-277,
01/15/1991
Copyright © 1991 by The American Society of Hematology
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|
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