Identification and molecular characterization of cellular factors required for glucocorticoid receptor-mediated mRNA decay

Ok Hyun Park, Joori Park, Mira Yu, Hyoung Tae An, Je Sang Ko, Yoon Ki Kim

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 thatGMDtriggers rapid degradation of targetmRNAsin a translation-independent and exon junction complexindependent 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, weshowthat HRSP12 plays an essential role in the formation of a functionally activeGMDcomplex. 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.

Original languageEnglish
Pages (from-to)2093-2105
Number of pages13
JournalGenes and Development
Volume30
Issue number18
DOIs
Publication statusPublished - 2016 Sep 15

Fingerprint

Glucocorticoid Receptors
RNA Stability
Y-Box-Binding Protein 1
Nonsense Mediated mRNA Decay
Endoribonucleases
Messenger RNA
RNA-Binding Proteins
Cytoplasmic and Nuclear Receptors
Proline
Protein Binding
Exons
Hot Temperature
Phosphorylation
Genome
Proteins

Keywords

  • Glucocorticoid receptor-mediated mRNA decay
  • HRSP12
  • PNRC2
  • UPF1
  • YBX1

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Identification and molecular characterization of cellular factors required for glucocorticoid receptor-mediated mRNA decay. / Park, Ok Hyun; Park, Joori; Yu, Mira; An, Hyoung Tae; Ko, Je Sang; Kim, Yoon Ki.

In: Genes and Development, Vol. 30, No. 18, 15.09.2016, p. 2093-2105.

Research output: Contribution to journalArticle

@article{20e56d328c924cc3a56d2284fb5fa957,
title = "Identification and molecular characterization of cellular factors required for glucocorticoid receptor-mediated mRNA decay",
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 thatGMDtriggers rapid degradation of targetmRNAsin a translation-independent and exon junction complexindependent 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, weshowthat HRSP12 plays an essential role in the formation of a functionally activeGMDcomplex. 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.",
keywords = "Glucocorticoid receptor-mediated mRNA decay, HRSP12, PNRC2, UPF1, YBX1",
author = "Park, {Ok Hyun} and Joori Park and Mira Yu and An, {Hyoung Tae} and Ko, {Je Sang} and Kim, {Yoon Ki}",
year = "2016",
month = "9",
day = "15",
doi = "10.1101/gad.286484.116",
language = "English",
volume = "30",
pages = "2093--2105",
journal = "Genes and Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press",
number = "18",

}

TY - JOUR

T1 - Identification and molecular characterization of cellular factors required for glucocorticoid receptor-mediated mRNA decay

AU - Park, Ok Hyun

AU - Park, Joori

AU - Yu, Mira

AU - An, Hyoung Tae

AU - Ko, Je Sang

AU - Kim, Yoon Ki

PY - 2016/9/15

Y1 - 2016/9/15

N2 - 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 thatGMDtriggers rapid degradation of targetmRNAsin a translation-independent and exon junction complexindependent 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, weshowthat HRSP12 plays an essential role in the formation of a functionally activeGMDcomplex. 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.

AB - 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 thatGMDtriggers rapid degradation of targetmRNAsin a translation-independent and exon junction complexindependent 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, weshowthat HRSP12 plays an essential role in the formation of a functionally activeGMDcomplex. 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.

KW - Glucocorticoid receptor-mediated mRNA decay

KW - HRSP12

KW - PNRC2

KW - UPF1

KW - YBX1

UR - http://www.scopus.com/inward/record.url?scp=84990942797&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84990942797&partnerID=8YFLogxK

U2 - 10.1101/gad.286484.116

DO - 10.1101/gad.286484.116

M3 - Article

C2 - 27798850

AN - SCOPUS:84990942797

VL - 30

SP - 2093

EP - 2105

JO - Genes and Development

JF - Genes and Development

SN - 0890-9369

IS - 18

ER -