Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10799152 | Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms | 2014 | 11 Pages |
Abstract
GR transcripts display a remarkable heterogeneity in their 5â² untranslated regions (5â²UTRs). These variable 5â²UTRs 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, 3â²-splicing, translation initiation and protein isoform production. We showed that these alternative 5â²UTRs influence the predicted mRNA structure and free energy, and were associated with differential levels of functional spliced mRNA. However, the 5â²UTR had little influence on the relative levels of the two principal 3â² 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 5â²UTR. 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 5â²UTRs has now been expanded to translational control, influencing total GR levels, individual constituent isoform levels, as well as trafficking to the cell surface.
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Authors
Jonathan D. Turner, Sara Vernocchi, Stephanie Schmitz, Claude P. Muller,