Glucocorticoid receptor interacts with PNRC2 in a ligand-dependent manner to recruit UPF1 for rapid mRNA degradation
- Authors
- Cho, Hana; Park, Ok Hyun; Park, Joori; Ryu, Incheol; Kim, Jeonghan; Ko, Jesang; Kim, Yoon Ki
- Issue Date
- 31-3월-2015
- Publisher
- NATL ACAD SCIENCES
- Keywords
- glucocorticoid receptor; PNRC2; UPF1; glucocorticoid receptor-mediated mRNA decay; Nonsense-mediated mRNA decay
- Citation
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.112, no.13, pp.E1540 - E1549
- Indexed
- SCIE
SCOPUS
- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Volume
- 112
- Number
- 13
- Start Page
- E1540
- End Page
- E1549
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/94077
- DOI
- 10.1073/pnas.1409612112
- ISSN
- 0027-8424
- 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.
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Collections - Graduate School > Department of Life Sciences > 1. Journal Articles
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