title: Novel splicing events and post-transcriptional regulation of human estrogen receptor α E isoforms.
abstract: Expression of the estrogen receptor α (ERα) 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 ERα E isoforms. We identified two novel untranslated exons, N1 and N2, in the 5'-region of the human ERα 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 ERα gene and the splicing profiles of the human ERα E isoforms are more complicated than previously reported. Furthermore, the 5'-UTRs of the E isoforms post-transcriptionally control human ERα expression mainly through translational repression.
authors.affiliation: Department of Physiology, Nippon Medical School, 1 Sendagi, Tokyo 113-8602, Japan. hirotaka@nms.ac.jp
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Ishii
authors.forename: Momoko
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Arisa
authors.initials: A
authors.lastname: Munetomo
authors.forename: Takenori
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Sakuma
mesh_terms: D020121:5' Untranslated Regions; D000328:Adult; D017398:Alternative Splicing; D001483:Base Sequence; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism; D061986:MCF-7 Cells; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010053:Ovary / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics; D012323:RNA Processing, Post-Transcriptional; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014599:Uterus / Q000378:metabolism; D055815:Young Adult
chemical_list: D020121:5' Untranslated Regions; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D020033:Protein Isoforms; D012333:RNA, Messenger