Pfeifer Ingrid, Anderson Curtis, Werner Rudolf, Oltra Elisa
Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, PO Box 016129, Miami, FL 33101, USA.
Nucleic Acids Res. 2004 Aug 24;32(15):4550-62. doi: 10.1093/nar/gkh792. Print 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.
连接蛋白43（cx43）基因最初被描述为由两个外显子组成，一个编码大部分5'-非翻译区（5'-UTR），另一个编码蛋白质序列和3'-UTR。我们现在报告，在小鼠中表达了另外四个外显子，均编码新的5'-UTR。我们总共发现了九种不同的cx43 mRNA种类（GenBank登录号NM010288以及AY427554至AY427561），它们是由不同的启动子使用和可变剪接机制产生的。这些不同mRNA的相对丰度随组织来源而变化。此外，不同的转录本在几种细胞系中表现出不同的翻译效率，表明存在调节cx43翻译的顺式RNA元件。我们提出，驱动cx43基因表达的启动子以细胞类型依赖的方式决定下游剪接事件中的外显子选择。这反过来又会影响转录本的翻译效率，从而协调导致cx43最终表达谱的事件。由于在大鼠中也观察到cx43基因的类似组织形式，因此涉及转录、剪接和翻译机制的cx43表达的复杂调控可能是进化过程中保守的共同特征。
