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

Abstract

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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Adrenergic control of cardiac gap junction function and expression

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Ultrastructural localization of connexins (Cx36, Cx43, Cx45), glutamate receptors and aquaporin-4 in rodent olfactory mucosa, olfactory nerve and olfactory bulb

“…Our miRNA data also suggest the need for caution in interpreting previous reporter gene experiments, either because some plasmid constructs did not contain the complete 3′ UTR of the original gene, or because the 3′ UTR was separated from the expressed portion of the gene by insertion of inappropriate termination sequences. It is now clear that more attention must be paid to the importance of 3′ UTRs, as well as 5′ UTRs, because both may be essential for cell-specific regulation of gene expression based on their influences on mRNA stability and post-transcriptional regulation of protein synthesis (Mignone et al, 2002;Pfeifer et al, 2004). Finally, it is increasingly apparent that expression of many genes may be hindered by endogenous miRNA mechanisms that are just beginning to be understood.…”