Novel splicing events and post-transcriptional regulation of human estrogen receptor α E isoforms

Expression of the estrogen receptor alpha (ER alpha) gene is subject to complex regulation. To elucidate the mechanisms of this regulation, the genomic organization and the physiological role of the multiple 5'-untranslated regions (5'-UTRs) must be determined. Here, we investigated the expression and splicing patterns of the human ER alpha E isoforms. We identified two novel untranslated exons, N1 and N2, in the 5'-region of the human ER alpha gene and multiple E isoform mRNA variants generated by alternative usage of non-coding internal exons. Expression of the N1-containing variants was observed only in the human breast adenocarcinoma cell line, MCF7, while the N2-containing variants were expressed in the adult liver and MCF7 cells. We examined post-transcriptional regulation of the variant mRNAs using luciferase reporter assays and quantitative PCR. The insertion of untranslated internal exons into the 5'-UTRs of the E isoforms reduced their translation efficiency, but barely influenced mRNA turnover. Our results indicate that the genomic organization of the human ER alpha gene and the splicing profiles of the human ER alpha E isoforms are more complicated than previously reported. Furthermore, the 5'-UTRs of the E isoforms post-transcriptionally control human ER alpha expression mainly through translational repression. (C) 2012 Elsevier Ltd. All rights reserved.