title: Role of the 5'-untranslated regions in post-transcriptional regulation of the human glucocorticoid receptor.
abstract: GR transcripts display a remarkable heterogeneity in their 5' untranslated regions (5'UTRs). These variable 5'UTRs are encoded by a series of alternative 1st exons, and together with their associated promoters they maintain tissue-specific GR expression levels. In this study we over-expressed GR transcripts containing individual 1st exons, and assessed their effect on RNA stability, 3'-splicing, translation initiation and protein isoform production. We showed that these alternative 5'UTRs influence the predicted mRNA structure and free energy, and were associated with differential levels of functional spliced mRNA. However, the 5'UTR had little influence on the relative levels of the two principal 3' splice transcripts, GR-α and -β. The overall mRNA length, the free energy of the transcript and the translational efficiency directly influenced total GR levels. However, individual N-terminal protein isoform levels appeared to depend upon elements within the 5'UTR. Membrane-GR specific labelling suggested that the mGR originates from transcripts containing exon 1D and possibly 1H, although the specific trafficking sequences or structures within these transcripts remain unidentified. The role of the alternative first exons and their associated 5'UTRs has now been expanded to translational control, influencing total GR levels, individual constituent isoform levels, as well as trafficking to the cell surface.
authors.affiliation: Institute of Immunology, Centre de Recherche Public de la Santé/Laboratoire National de Santé, 20A rue Auguste Lumière, L-1950 Luxembourg, Luxembourg.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Turner
authors.affiliation: Institute of Immunology, Centre de Recherche Public de la Santé/Laboratoire National de Santé, 20A rue Auguste Lumière, L-1950 Luxembourg, Luxembourg; Department of Immunology, Research Institute of Psychobiology, University of Trier, D-54290 Trier, Germany.
authors.forename: Sara
authors.initials: S
authors.lastname: Vernocchi
authors.affiliation: Institute of Immunology, Centre de Recherche Public de la Santé/Laboratoire National de Santé, 20A rue Auguste Lumière, L-1950 Luxembourg, Luxembourg.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Schmitz
authors.affiliation: Institute of Immunology, Centre de Recherche Public de la Santé/Laboratoire National de Santé, 20A rue Auguste Lumière, L-1950 Luxembourg, Luxembourg; Department of Immunology, Research Institute of Psychobiology, University of Trier, D-54290 Trier, Germany. Electronic address: claude.muller@CRP-SANTE.LU.
authors.forename: Claude P
authors.initials: CP
authors.lastname: Muller
mesh_terms: D020121:5' Untranslated Regions; D017398:Alternative Splicing; D006207:Half-Life; D006801:Humans; D009690:Nucleic Acid Conformation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics; D020871:RNA Stability; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D020121:5' Untranslated Regions; D020033:Protein Isoforms; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid
keywords: Glucocorticoid receptor; RNA stability; Transcriptional isoforms; Translational efficiency; Translational isoforms