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 transcriptionally 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-globin mRNA has been identified. The present work describes an mRNP complex assembling on the 3' UTR of the beta-globin mRNA that exhibits many of the properties of the stability-enhancing alpha complex. The beta-globin mRNP complex is shown to contain one or more factors homologous to alphaCP, a 39-kDa RNA-binding protein that is integral to alpha-complex assembly. Sequence analysis implicates a specific 14-nucleotide pyrimidine-rich track within its 3' UTR as the site of beta-globin mRNP assembly. The importance of this track to mRNA stability is subsequently verified in vivo using mice expressing human beta-globin transgenes that contain informative mutations in this region. In combination, the in vitro and in vivo analyses indicate that the high stabilities of the alpha- and beta-globin mRNAs are maintained through related mRNP complexes that may share a common regulatory pathway.
Yu
J
J
Department of Medicine (Hematology/Oncology), University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Russell
J E
JE
D020413:3' Untranslated Regions / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D005914:Globins / Q000235:genetics*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D020871:RNA Stability; D012261:Ribonucleoproteins / Q000378:metabolism*; D013329:Structure-Activity Relationship
D020413:3' Untranslated Regions; D012261:Ribonucleoproteins; C026452:messenger ribonucleoprotein; D005914:Globins