Detection and characterization of a 3' untranslated region ribonucleoprotein complex associated with human α-globin mRNA stability

X. Wang, Megerditch Kiledjian, I. M. Weiss, S. A. Liebhaber

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Abstract

The highly stable nature of globin mRNA is of central importance to erythroid cell differentiation. We have previously identified cytidine-rich (C-rich) segments in the human α-globin mRNA 3' untranslated region (α- 3'UTR) which are critical in the maintenance of mRNA stability in transfected erythroid cells. In the present studies, we have detected trans-acting factors which interact with these cis elements to mediate this stabilizing function. A sequence-specific ribonucleoprotein (RNP) complex is assembled after incubation of the α-3'UTR with a variety of cytosolic extracts. This so-called α-complex is sequence specific and is not formed on the 3'UTR of either β-globin or growth hormone mRNAs. Furthermore, base substitutions within the C-rich stretches which destabilize α-globin mRNA in vivo result in a parallel disruption of the α-complex in vitro. Competition studies with a series of homoribopolymers reveals a striking sensitivity of α-complex formation to poly(C), suggesting the presence of a poly(C)-binding activity within the α-complex. Three predominant proteins are isolated by α-3'UTR affinity chromatography. One of these binds directly to poly(C). This cytosolic poly(C)-binding protein is distinct from previously described nuclear poly(C)-binding heterogeneous nuclear RNPs and is necessary but not sufficient for α-complex formation. These data suggest that a messenger RNP complex formed by interaction of defined segments within the α-3'UTR with a limited number of cytosolic proteins, including a potentially novel poly(C)- binding protein, is of functional importance in establishing high-level stability of α-globin mRNA.

Original languageEnglish (US)
Pages (from-to)1769-1777
Number of pages9
JournalMolecular and cellular biology
Volume15
Issue number3
DOIs
StatePublished - 1995

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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