A Tri-Nucleotide Pattern in a 3’ Utr Segment Affects the Activity of a Human Glucocorticoid Receptor Isoform

Tajia L. Green, Stacey M. Leventhal, Debora Lim, Kiho Cho, David G Greenhalgh

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


ABSTRACT: We previously identified a truncated human glucocorticoid receptor (hGR) isoform of 118 amino acids, hGR-S1(-349A), that despite lacking the major functional domains, was more hyperactive after glucocorticoid treatment than the full-length receptor. Furthermore, its 3’ untranslated region (UTR) was required. To dissect the underlying mechanisms for hyperactivity, a series of hGR isoforms with consecutive deletions in the 3’ UTR were created to test their transactivation potential using reporter assays. The hGR-S1(-349A) isoform retaining 1303?bp of 3’ UTR displayed unusually high activity with or without glucocorticoid stimulation. Unexpectedly, a complete loss of significant activity was observed with isoforms retaining 1293?bp or 1263?bp of 3’ UTR. Analysis of the 20?bp region neighboring the 1293?bp site showed a pattern: 3’UTR termination at every third base pair in this region resulted in a loss of transactivation potential while the other sites retained hyperactivity with or without glucocorticoid stimulation. Variations in the activity of an hGR isoform, due to changes in the 3’ UTR sequence configuration, may provide an important link in explaining inconsistent responses to glucocorticoid treatment in individuals and ultimately enable tailored, patient specific care. Furthermore, understanding the mechanisms underlying the cyclic hyperactivity/loss of activity phenomenon may be a step towards identifying a novel mechanism of gene regulation.

Original languageEnglish (US)
StateAccepted/In press - Sep 22 2016

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine


Dive into the research topics of 'A Tri-Nucleotide Pattern in a 3’ Utr Segment Affects the Activity of a Human Glucocorticoid Receptor Isoform'. Together they form a unique fingerprint.

Cite this