Shared stabilization functions of pyrimidine-rich determinants in the erythroid 15-lipoxygenase and α-globin mRNAs

The poly(C)-binding proteins, alpha 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 alpha CP function link these controls to late stages of erythroid differentiation: translational silencing of 15-lipoxygenase (Lox) mRNA and stabilization of alpha-globin mRNA. These two controls are mediated via association of alpha CPs with structurally related C-rich 3'-untranslated region elements: the differentiation control elements (DICE) in Lox mRNA and the pyrimidine-rich motifs in alpha-globin mRNA. In the present report a set of mRNA translation and stability assays are used to determine how these two alpha 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 alpha CP decoy but not by the same decoy restricted to the cytoplasm. These data support a general role for alpha CPs in stabilizing a subset of erythroid mRNAs. The findings also suggest that initial binding of alpha 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.