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Nucleic Acids Research 2004 32(15):4550-4562; doi:10.1093/nar/gkh792
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Published online 24 August 2004

Nucleic Acids Research, Vol. 32 No. 15 © Oxford University Press 2004; all rights reserved

Redefining the structure of the mouse connexin43 gene: selective promoter usage and alternative splicing mechanisms yield transcripts with different translational efficiencies

Ingrid Pfeifer, Curtis Anderson, Rudolf Werner and Elisa Oltra*

Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, PO Box 016129, Miami, FL 33101, USA

* To whom correspondence should be addressed. Tel: +1 305 243 6998; Fax: +1 305 243 3065; Email: eoltra{at}molbio.med.miami.edu
+AY427554–AY427561, AY555736–AY555740

Received July 13, 2004; Revised and Accepted August 8, 2004

The connexin43 (cx43) gene was originally described as consisting of two exons, one coding for most of the 5'-untranslated region (5'-UTR), and the other for the protein sequence and 3'-UTR. We now report that in mouse four additional exons are expressed, all coding for novel 5'-UTRs. Altogether, we found nine different cx43 mRNA species (GenBank accession numbers NM010288, and AY427554 through AY427561) generated by differential promoter usage and alternative splicing mechanisms. The relative abundance of these different mRNAs varied with the tissue source. In addition, the different transcripts showed varying translational efficiencies in several cell lines, indicating the presence of cis-RNA elements that regulate cx43 translation. We propose that it is the promoter driving the expression of the cx43 gene that determines exon choice in the downstream splicing events in a cell-type-dependent fashion. This in turn will affect the translation efficiency of the transcript orchestrating the events that lead to the final expression profile of cx43. Since a similar organization of the cx43 gene was also observed in rat it is likely that the complex regulation of cx43 expression involving transcription, splicing and translation mechanisms is a common trait conserved during evolution.


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