Identification and molecular characterization of cellular factors required for glucocorticoid receptor-mediated mRNA decay
- Authors
- Park, Ok Hyun; Park, Joori; Yu, Mira; An, Hyoung-Tae; Ko, Jesang; Kim, Yoon Ki
- Issue Date
- 15-9월-2016
- Publisher
- COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
- Keywords
- glucocorticoid receptor-mediated mRNA decay; YBX1; HRSP12; UPF1; PNRC2
- Citation
- GENES & DEVELOPMENT, v.30, no.18, pp.2093 - 2105
- Indexed
- SCIE
SCOPUS
- Journal Title
- GENES & DEVELOPMENT
- Volume
- 30
- Number
- 18
- Start Page
- 2093
- End Page
- 2105
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/87507
- DOI
- 10.1101/gad.286484.116
- ISSN
- 0890-9369
- Abstract
- Glucocorticoid (GC) receptor (GR) has been shown recently to bind a subset of mRNAs and elicit rapid mRNA degradation. However, the molecular details of GR-mediated mRNA decay (GMD) remain unclear. Here, we demonstrate that GMD triggers rapid degradation of target mRNAs in a translation-independent and exon junction complex independent manner, confirming that GMD is mechanistically distinct from nonsense-mediated mRNA decay (NMD). Efficient GMD requires PNRC2 (proline-rich nuclear receptor coregulatory protein 2) binding, helicase ability, and ATM-mediated phosphorylation of UPF1 (upstream frameshift 1). We also identify two GMD-specific factors: an RNA-binding protein, YBX1 (Y-box-binding protein 1), and an endoribonuclease, HRSP12 (heat-responsive protein 12). In particular, using HRSP12 variants, which are known to disrupt trimerization of HRSP12, we show that HRSP12 plays an essential role in the formation of a functionally active GMD complex. Moreover, we determine the hierarchical recruitment of GMD factors to target mRNAs. Finally, our genome-wide analysis shows that GMD targets a variety of transcripts, implicating roles in a wide range of cellular processes, including immune responses.
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