Structural and functional analysis of an mRNP complex that mediates the high stability of human beta-globin mRNA

Human globins are encoded by mRNAs exhibiting high stabilities in transcrip tionally silenced erythrocyte progenitors. Unlike alpha -globin mRNA, whose stability is enhanced by assembly of a specific messenger RNP (mRNP) alpha complex on its 3' untranslated region (UTR), neither the structure(s) nor the mechanism(s) that effects the high-level stability of human beta -globi n mRNA has been identified. The present work describes an mRNP complex asse mbling on the 3' UTR of the beta -globin mRNA that exhibits many of the pro perties of the stability-enhancing alpha complex. The beta -globin mRNP com plex is shown to contain one or more factors homologous to alpha CP, a 39-k Da RNA-binding protein that is integral to alpha -complex assembly. Sequenc e analysis implicates a specific 14-nucleotide pyrimidine-rich track within its 3' UTR as the site of beta -globin mRNP assembly. The importance of th is track to mRNA stability is subsequently verified in vivo using mice expr essing human beta -globin transgenes that contain informative mutations in this region. In combination, the in vitro and in vivo analyses indicate tha t the high stabilities of the alpha- and beta -globin mRNAs are maintained through related mRNP complexes that may share a common regulatory pathway.