title: Glucocorticoid receptor interacts with PNRC2 in a ligand-dependent manner to recruit UPF1 for rapid mRNA degradation.
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.
authors.affiliation: Division of Life Sciences, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Hana
authors.initials: H
authors.lastname: Cho
authors.affiliation: Division of Life Sciences, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Ok Hyun
authors.initials: OH
authors.lastname: Park
authors.affiliation: Division of Life Sciences, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Joori
authors.initials: J
authors.lastname: Park
authors.affiliation: Division of Life Sciences, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Incheol
authors.initials: I
authors.lastname: Ryu
authors.affiliation: Division of Life Sciences, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Jeonghan
authors.initials: J
authors.lastname: Kim
authors.affiliation: Division of Life Sciences, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Jesang
authors.initials: J
authors.lastname: Ko
authors.affiliation: Division of Life Sciences, Korea University, Seoul 136-701, Republic of Korea yk-kim@korea.ac.kr.
authors.forename: Yoon Ki
authors.initials: YK
authors.lastname: Kim
mesh_terms: D018932:Chemokine CCL2 / Q000378:metabolism; D002633:Chemotaxis; D017930:Genes, Reporter; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D009000:Monocytes / Q000378:metabolism; D059365:Nonsense Mediated mRNA Decay; D011485:Protein Binding; D020365:RNA Helicases; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D008024:Ligands; C437718:PNRC2 protein, human; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011965:Receptors, Glucocorticoid; D015534:Trans-Activators; D014157:Transcription Factors; D020365:RNA Helicases; C101828:UPF1 protein, human
keywords: Nonsense-mediated mRNA decay; PNRC2; UPF1; glucocorticoid receptor; glucocorticoid receptor-mediated mRNA decay