Identification of AUF1 (heterogeneous nuclear ribonucleoprotein D) as a component of the α-globin mRNA stability complex

mRNA turnover is an important regulatory component of gene expression and is significantly influenced by ribonucleoprotein (RNP) complexes which form on the mRNA. Studies of human α-globin mRNA stability have identified a specific RNP complex (α-complex) which forms on the 3' untranslated region (3'UTR) of the mRNA and appears to regulate the erythrocyte-specific accumulation of α-globin mRNA. One of the protein activities in this multiprotein complex is a poly(C)-binding activity which consists of two proteins, αCP1 and αCP2. Neither of these proteins, individually or as a pair, can bind the α-globin 3'UTR unless they are complexed with the remaining non-poly(C) binding proteins of the α-complex. With the yeast two- hybrid screen, a second α-complex protein was identified. This protein is n member of the previously identified A+U-rich (ARE) binding/degradation factor (AUF1) family of proteins, which are also known as the heterogeneous nuclear RNP (hnRNP) D proteins. We refer to these proteins as AUF1/hnRNP-D. Thus, a protein implicated in ARE-mediated mRNA decay is also an integral component of the mRNA stabilizing α-complex. The interaction of AUF1/hnRNP-D is more efficient with αCP1 relative to αCP2 both in vitro and in vivo, suggesting that the α-complex might be dynamic rather than a fixed complex. AUF1/hnRNP- D could, therefore, be a general mRNA turnover factor involved in both stabilization and decay of mRNA.