Role of the 5'-untranslated regions in post-transcriptional regulation of the human glucocorticoid receptor

Jonathan D. Turner, Sara Vernocchi, Stephanie Schmitz, Claude P. Muller*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

34 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1051-1061
Number of pages11
JournalBiochimica et Biophysica Acta - Gene Regulatory Mechanisms
Volume1839
Issue number11
DOIs
Publication statusPublished - 19 Aug 2014

Keywords

  • Glucocorticoid receptor
  • RNA stability
  • Transcriptional isoforms
  • Translational efficiency
  • Translational isoforms

Fingerprint

Dive into the research topics of 'Role of the 5'-untranslated regions in post-transcriptional regulation of the human glucocorticoid receptor'. Together they form a unique fingerprint.

Cite this