The 5'-untranslated regions (5'-UTRs) of the estrogen receptor α (ERα) mRNAs play important roles in the modulation of translation. To elucidate the mechanisms regulating human ERα gene expression, it is necessary to determine its genomic organization and the roles of the multiple 5'-UTRs. We therefore examined the splicing and expression profiles of the human ERα F isoforms. A novel non-coding exon E3 was found in the 5'-region of the human ERα gene and six F isoform mRNA variants were identified. The variants revealed the preferred expression patterns. Post-transcriptional regulation was also investigated. The 5'-UTRs of the F isoforms decreased the translation efficiency but had no effect on mRNA stability. The results indicate that the organization and splicing patterns of the human ERα gene are more complex than previously reported, and that the 5'-UTRs of the F isoforms contribute to the post-transcriptional control of human ERα gene expression through translation repression.
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