The 3′ Untranslated Region Complex Involved in Stabilization of Human α-globin mRNA Assembles in the Nucleus and Serves an Independent Role as a Splice Enhancer
- 1 May 2007
- journal article
- research article
- Published by Taylor & Francis Ltd in Molecular and Cellular Biology
- Vol. 27 (9), 3290-3302
- https://doi.org/10.1128/mcb.02289-05
Abstract
Posttranscriptional controls, mediated primarily by RNA-protein complexes, have the potential to alter multiple steps in RNA processing and function. Human α-globin mRNA is bound at a C-rich motif in the 3′ untranslated region (3′UTR) by the KH domain protein α-globin poly(C)-binding protein (αCP). This “α-complex” is essential to cytoplasmic stability of α-globin mRNA in erythroid cells. Here we report that the 3′UTR α-complex also serves an independent nuclear role as a splice enhancer. Consistent with this role, we find that αCP binds α-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 αCP 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 αCP complex may serve to “prepackage” α-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.Keywords
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