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Role of AUUU sequences in stabilization of granulocyte-macrophage
colony-stimulating factor RNA in stimulated cells
M Akashi, G Shaw, M Gross, M Saito and HP Koeffler
Center for Health Sciences, UCLA School of Medicine 90024-1678.
RNAs for transiently expressed genes such as oncogenes and cytokines,
including granulocyte-monocyte colony-stimulating factor (GM-CSF), have a
short half-life (T1/2). A cluster of AUUU sequences identified in the 3'
untranslated (UT) region of these RNAs has been implicated in controlling
stability of these transcripts. We examined the role of AUUU sequences in
mRNA stability of GM-CSF after stimulation of cells. Human fibroblasts
(W138) were stably transfected with chimeric constructs containing the
beta-globin gene linked to a 52-bp tail of GM- CSF containing either eight
ATTTT (pNEOR beta G-AT) or eight repeats in which the AT sequences have
been changed to GC sequences (pNEOR beta G- GC). Data confirmed that AUUU
sequences in 3'UT region of GM-CSF play a major role in GM-CSF RNA
instability. Stimulators of protein kinase C (PKC), cycloheximide (CHX),
sodium fluoride (NaF), and, to a more limited extent, interleukin-1 beta
(IL-1 beta), appear to stabilize GM- CSF RNA through these AUUU sequences,
but tumor necrosis factor-alpha (TNF-alpha) induces stabilization of GM-CSF
RNA through a mechanism independent of their AUUU sequences.
Volume 78,
Issue 8,
pp. 2005-2012,
10/15/1991
Copyright © 1991 by The American Society of Hematology
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