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Mol. Cell. Biol. doi:10.1128/MCB.02289-05
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The 3'UTR Complex Involved in Stabilization of Human -Globin mRNA Assembles in the Nucleus and Serves an Independent Role as Splice-Enhancer

Departments of Genetics and Medicine and Department of Medicine, Renal-Electrolyte and Hypertension Division, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, 19104 USA

^* To whom correspondence should be addressed. Email: liebhabe{at}mail.med.upenn.edu.

	Abstract

Post-transcriptional controls, mediated primarily by RNA-protein complexes, have the potential to alter multiple steps in RNA processing and function. Human -globin mRNA is bound at a C-rich motif in the 3'UTR by the KH-domain protein, CP. This ‘-complex’ is essential to cytoplasmic stability of -globin mRNA in erythroid cells. Here we report that the 3'UTR -complex also serves an independent nuclear role as a splice-enhancer. Consistent with this role, we find that CP binds -globin transcripts prior to splicing. Surprisingly, this binding occurs at C-rich sites within intron I as well as at the 3'UTR C-rich determinant. The intronic and 3'UTR CP complexes appear to have distinct effects on splicing. While intron I complexes repress intron I excision, the 3'UTR complex enhances splicing of the full-length transcript both in vivo and in vitro. In addition to its importance to splicing, nuclear assembly of the 3'UTR CP complex may serve to ‘prepackage’ -globin mRNA with its stabilizing complex prior to cytoplasmic export. Linking nuclear and cytoplasmic controls by the action of a particular RNA-binding protein, as reported here, may represent a modality of general importance in eukaryotic gene regulation.

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