Complementary change in cis determinants and trans factors in the evolution of an mRNP stability complex.
RNA-protein (RNP) complexes play significant roles in the fate and expression of mRNAs. The prolonged half-life of human alpha-globin mRNA, a major determinant of normal erythroid differentiation, is dependent on the assembly of a sequence-specific 3'-untranslated region (3'UTR) RNP (alpha-complex). We demonstrate that the stability of murine alpha-globin mRNA is controlled by a parallel mechanism. Unexpectedly, however, the respective 3'UTR RNP complexes that stabilize the h(alpha)- and m(alpha)-globin mRNAs differ in structure. While the cis determinants in both species are encoded in polypyrimidine tracks, the human determinant is C-rich (CCUCC motif) while the mouse alpha-3'UTR consists of an equal distribution of Cs and Us (CCUUCU motif). The protein components of the corresponding human and murine alpha-complexes differ in a complementary manner: the previously described 39 kDa poly(C) binding protein (PCBP) present in the human alpha-complex is replaced in the mouse alpha-complex by a 48 kDa cytoplasmic poly(CU) binding protein (CUBP). These results reveal that drift in the primary sequences of the alpha-globin mRNA 3'UTR polypyrimidine tracks in a comparison between mouse and human is paralleled by an alteration in the composition of the corresponding trans-acting components. Surprisingly, these structurally distinct complexes appear to perform the identical function of stabilizing the corresponding alpha-globin mRNAs.
Wang
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Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Liebhaber
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D000818:Animals; D001483:Base Sequence; D003600:Cytosol / Q000378:metabolism; D005914:Globins / Q000235:genetics; D006207:Half-Life; D006367:HeLa Cells; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D011066:Poly C / Q000378:metabolism; D011072:Poly U / Q000378:metabolism; D038941:Polypyrimidine Tract-Binding Protein; D011743:Pyrimidines / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D012261:Ribonucleoproteins / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D011743:Pyrimidines; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; C026452:messenger ribonucleoprotein; D038941:Polypyrimidine Tract-Binding Protein; C035610:poly(U-C); D011072:Poly U; D011066:Poly C; D005914:Globins; C030986:pyrimidine