title: Shared stabilization functions of pyrimidine-rich determinants in the erythroid 15-lipoxygenase and alpha-globin mRNAs.
abstract: The poly(C)-binding proteins, alphaCPs, 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 alphaCP 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 alphaCPs 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 alphaCP-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 alphaCP decoy but not by the same decoy restricted to the cytoplasm. These data support a general role for alphaCPs in stabilizing a subset of erythroid mRNAs. The findings also suggest that initial binding of alphaCP 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.
authors.affiliation: Department of Genetics and Medicine, University of Pennsylvania School of Medicine, Room 428 CRB, 415 Curie Blvd., Philadelphia, PA 19104, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Kong
authors.forename: Marina
authors.initials: M
authors.lastname: Sumaroka
authors.forename: Dawn L
authors.initials: DL
authors.lastname: Eastmond
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Liebhaber
mesh_terms: D020413:3' Untranslated Regions; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism* / Q000502:physiology*; D017930:Genes, Reporter; D005914:Globins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D038941:Polypyrimidine Tract-Binding Protein / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D011743:Pyrimidines / Q000378:metabolism*; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D020218:Response Elements
chemical_list: D020413:3' Untranslated Regions; D011743:Pyrimidines; D012333:RNA, Messenger; D038941:Polypyrimidine Tract-Binding Protein; D005914:Globins; D001093:Arachidonate 15-Lipoxygenase