Complementary change in cis determinants and trans factors in the revolution of an mRNP stability complex

Abstract

RNA-protein (RNP) complexes play significant roles in the fate and expression of mRNAs. The prolonged half-life of human α-globin mRNA, a major determinant of normal erythroid differentiation, is dependent on the assembly of a sequence-specific 3'-untranslated region (3'UTR) RNP (α-complex). We demonstrate that the stability of murine α-globin mRNA is controlled by a parallel mechanism. Unexpectedly, however, the respective 3'UTR RNP complexes that stabilize the hα- and mα-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 α-3'UTR consists of an equal distribution of Cs and Us (CCUUCU motif). The protein components of the corresponding human and murine α-complexes differ in a complementary manner: the previously described 39 kDa poly(C) binding protein (PCBP) present in the human α-complex is replaced in the mouse α-complex by a 48 kDa cytoplasmic poly(CU) binding protein (CUBP). These results reveal that drift in the primary sequences of the α-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 α-globin mRNAs.