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Molecular and Cellular Biology, August 2006, p. 5603-5614, Vol. 26, No. 15
0270-7306/06/$08.00+0     doi:10.1128/MCB.01845-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Shared Stabilization Functions of Pyrimidine-Rich Determinants in the Erythroid 15-lipoxygenase and -globin mRNAs

Jian Kong, Marina Sumaroka, Dawn L. Eastmond, and Stephen A. Liebhaber^*

Departments of Genetics and Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

Received 20 September 2005/ Returned for modification 17 October 2005/ Accepted 12 May 2006

The poly(C)-binding proteins, CPs, comprise a set of highly conserved KH-domain factors that participate in mRNA stabilization and translational controls in developmental and viral systems. Two prominent models of CP function link these controls to late stages of erythroid differentiation: translational silencing of 15-lipoxygenase (Lox) mRNA and stabilization of -globin mRNA. These two controls are mediated via association of CPs with structurally related C-rich 3'-untranslated region elements: the differentiation control elements (DICE) in Lox mRNA and the pyrimidine-rich motifs in -globin mRNA. In the present report a set of mRNA translation and stability assays are used to determine how these two CP-containing complexes, related in structure and position, mediate distinct posttranscriptional controls. While the previously reported translational silencing by the DICE is not evident in our studies, we find that the two determinants mediate similar levels of mRNA stabilization in erythroid cells. In both cases this stabilization is sensitive to interference by a nuclear-restricted CP decoy but not by the same decoy restricted to the cytoplasm. These data support a general role for CPs in stabilizing a subset of erythroid mRNAs. The findings also suggest that initial binding of CP to target mRNAs occurs in the nucleus. Assembly of stabilizing mRNP complexes in the nucleus prior to export may maximize their impact on cytoplasmic events.

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* Corresponding author. Mailing address: Departments of Genetics and Medicine, University of Pennsylvania School of Medicine, Room 428 CRB, 415 Curie Blvd., Philadelphia, PA 19104. Phone: (215) 898-7834. Fax: (215) 573-5157. E-mail: liebhabe{at}mail.med.upenn.edu.

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Molecular and Cellular Biology, August 2006, p. 5603-5614, Vol. 26, No. 15
0270-7306/06/$08.00+0     doi:10.1128/MCB.01845-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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