Glucocorticoid receptor interacts with PNRC2 in a ligand-dependent manner to recruit UPF1 for rapid mRNA degradation

Hana Cho, Ok Hyun Park, Joori Park, Incheol Ryu, Jeonghan Kim, Je Sang Ko, Yoon Ki Kim

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Glucocorticoid receptor (GR), which was originally known to function as a nuclear receptor, plays a role in rapid mRNA degradation by acting as an RNA-binding protein. The mechanism by which this process occurs remains unknown. Here, we demonstrate that GR, preloaded onto the 5?UTR of a target mRNA, recruits UPF1 through proline-rich nuclear receptor coregulatory protein 2 (PNRC2) in a ligand-dependent manner, so as to elicit rapid mRNA degradation. We call this process GR-mediated mRNA decay (GMD). Although GMD, nonsense-mediated mRNA decay (NMD), and staufen-mediated mRNA decay (SMD) share upstream frameshift 1 (UPF1) and PNRC2, we find that GMD is mechanistically distinct from NMD and SMD. We also identify de novo cellular GMD substrates using microarray analysis. Intriguingly, GMD functions in the chemotaxis of human monocytes by targeting chemokine (C-C motif) ligand 2 (CCL2) mRNA. Thus, our data provide molecular evidence of a posttranscriptional role of the well-studied nuclear hormone receptor, GR, which is traditionally considered a transcription factor.

Original languageEnglish
Pages (from-to)E1540-E1549
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number13
DOIs
Publication statusPublished - 2015 Mar 31

Keywords

  • Glucocorticoid receptor
  • Glucocorticoid receptor-mediated mrna decay
  • Nonsense-mediated mrna decay
  • PNRC2
  • UPF1

ASJC Scopus subject areas

  • General

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