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Molecular and Cellular Biology, February 2003, p. 1125-1134, Vol. 23, No. 4
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.4.1125-1134.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

The KH-Domain Protein CP Has a Direct Role in mRNA Stabilization Independent of Its Cognate Binding Site

Departments of Genetics and Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

Received 21 August 2002/ Returned for modification 1 October 2002/ Accepted 13 November 2002

Previous studies suggest that high-level stability of a subset of mammalian mRNAs is linked to a C-rich motif in the 3' untranslated region (3'UTR). High-level expression of human -globin mRNA (h-globin mRNA) in erythroid cells has been specifically attributed to formation of an RNA-protein complex comprised of a 3'UTR C-rich motif and an associated 39-kDa poly(C) binding protein, CP. Documentation of this RNA-protein -complex has been limited to in vitro binding studies, and its impact has been monitored by alterations in steady-state mRNA. Here we demonstrate that CP is stably bound to h-globin mRNA in vivo, that -complex assembly on the h-globin mRNA is restricted to the 3'UTR C-rich motif, and that -complex assembly extends the physical half-life of h-globin mRNA selectively in erythroid cells. Significantly, these studies also reveal that an artificially tethered CP has the same mRNA-stabilizing activity as the native -complex. These data demonstrate a unique contribution of the -complex to h-globin mRNA stability and support a model in which the sole function of the C-rich motif is to selectively tether CP to a subset of mRNAs. Once bound, CP appears to be fully sufficient to trigger downstream events in the stabilization pathway.

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