Affiliation:
1. Departments of Genetics and Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104
Abstract
ABSTRACT
The poly(C)-binding proteins, αCPs, 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 αCP function link these controls to late stages of erythroid differentiation: translational silencing of
15-lipoxygenase
(
Lox
) mRNA and stabilization of α
-globin
mRNA. These two controls are mediated via association of αCPs with structurally related C-rich 3′-untranslated region elements: the differentiation control elements (DICE) in
Lox
mRNA and the pyrimidine-rich motifs in α-
globin
mRNA. In the present report a set of mRNA translation and stability assays are used to determine how these two αCP-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 αCP decoy but not by the same decoy restricted to the cytoplasm. These data support a general role for αCPs in stabilizing a subset of erythroid mRNAs. The findings also suggest that initial binding of αCP 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.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Cited by
16 articles.
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