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Vol. 13, No. 14, pp. 1884-1897, July 15, 1999
Department of Biochemistry and Molecular Biology, The University of
Texas Houston Health Science Center, Medical School,
Houston, Texas 77030 USA
AU-rich RNA-destabilizing elements (AREs) have become a paradigm for
studying cytoplasmic mRNA turnover in mammalian cells. Though many
RNA-binding proteins have been shown to bind to AREs in vitro,
trans-acting factors that participate in the in vivo destabilization of cytoplasmic RNA by AREs remains unknown. Experiments were performed to investigate the cellular mechanisms and to identify potential trans-acting factors for ARE-directed mRNA decay.
These experiments identified hnRNP D, a heterogeneous nuclear
ribonucleoprotein (hnRNP) capable of shuttling between the nucleus and
cytoplasm, as an RNA destabilizing protein in vivo in ARE-mediated
rapid mRNA decay. Our results show that the ARE destabilizing function is dramatically impeded during hemin-induced erythroid differentiation and not in TPA-induced megakaryocytic differentiation of human erythroleukemic K562 cells. A sequestration of hnRNP D into a hemin-induced protein complex, termed hemin-regulated factor or HRF,
correlates well with the loss of ARE-destabilizing function in the
cytoplasm. Further experiments show that in hemin-treated cells,
ectopic expression of hnRNP D restores the rapid decay directed by the
ARE. The extent of destabilizing effect varies among the four isoforms
of hnRNP D, with p37 and p42 displaying the most profound effect. These
results demonstrate a specific cytoplasmic function for hnRNP D as an
RNA-destabilizing protein in ARE-mediated decay pathway. These in vivo
findings support an emerging idea that shuttling hnRNP proteins have
not only a nuclear but also a cytoplasmic function in mRNA metabolism.
The data further imply that shuttling hnRNP proteins define, at least in part, the nuclear history of individual mRNAs and thereby influence their cytoplasmic fate.
[Key Words: AU-rich element; hnRNP protein; mRNA turnover; tetracycline-regulatory system; hematopoietic differentiation]
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|
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|
|
|
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|
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|
|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
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|
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|
|
|
|
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