title: Differential regulation and function of 5'-untranslated GR-exon 1 transcripts.
abstract: Alternative splicing serves to increase biological diversity and adaptation. Many genes, including the glucocorticoid receptor (GR), contain multiple 5'-untranslated exons in their promoter regions that can give rise to various mRNA isoforms encoding the same protein. To date, information on the mouse GR promoter remains sparse. Here, we extensively characterize alternative first exons of the mouse GR to reveal homology to the rat and human. We further find that, although most promoters are broadly expressed in various tissues, transcription of individual promoters can be differentially regulated by growth factor- and depolarization-induced signaling. Moreover, in addition to selective promoter usage, the alternative first exon transcripts differentially control RNA stability and translation efficiency, indicative of their role in GR expression. In conclusion, the composite GR promoter enables multilayered adjustments in gene expression through transcriptional and posttranscriptional mechanisms that may serve varying physiological demands.
authors.affiliation: Neuroadaptations Group, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Bockmühl
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Murgatroyd
authors.forename: Arleta
authors.initials: A
authors.lastname: Kuczynska
authors.forename: Ian M
authors.initials: IM
authors.lastname: Adcock
authors.forename: Osborne F X
authors.initials: OF
authors.lastname: Almeida
authors.forename: Dietmar
authors.initials: D
authors.lastname: Spengler
mesh_terms: D020121:5' Untranslated Regions; D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D005091:Exons; D005786:Gene Expression Regulation; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D009690:Nucleic Acid Conformation; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013154:Spleen / Q000378:metabolism; D013950:Thymus Gland / Q000378:metabolism
chemical_list: D020121:5' Untranslated Regions; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid