{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nHuman PNRC2 was originally identified as a nuclear receptor co‐regulator when it was shown to interact directly with estrogen‐related receptor gamma, functioning as a coactivator in a transcriptional complex that also involves the bHLH corepressor TLE1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " \n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSubsequent studies in the context of mRNA surveillance have demonstrated that PNRC2 serves as an adaptor linking the nonsense‐mediated mRNA decay (NMD) machinery with the decapping complex. In these investigations, PNRC2 was found to preferentially associate with hyperphosphorylated UPF1 and interact via distinct motifs with the decapping factor Dcp1a—its proline‐rich region binding the EVH1 domain of Dcp1a and its NR‐box mediating the UPF1 interaction."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " These interactions promote the localization of aberrant messenger ribonucleoproteins into processing bodies and stimulate decapping activity by bridging Dcp1a and Dcp2. Notably, despite its decapping coactivator role facilitating 5′–3′ exonucleolytic decay in tethering assays, subsequent work has raised questions about the absolute requirement for PNRC2 in canonical NMD."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurther extending its functional portfolio, PNRC2 also participates in a distinct mRNA decay pathway. In a mechanism termed GR-mediated mRNA decay (GMD), the glucocorticoid receptor, preloaded onto the 5′UTR of target transcripts, recruits UPF1 via PNRC2 in a ligand-dependent manner, thereby eliciting rapid mRNA degradation and influencing cellular responses such as monocyte chemotaxis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Moritz Hentschke, Uwe Borgmeyer "}, {"type": "b", "children": [{"type": "t", "text": "Identification of PNRC2 and TLE1 as activation function-1 cofactors of the orphan nuclear receptor ERRgamma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2003.11.025"}], "href": "https://doi.org/10.1016/j.bbrc.2003.11.025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14651967"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14651967"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Hana Cho, Kyoung Mi Kim, Yoon Ki Kim "}, {"type": "b", "children": [{"type": "t", "text": "Human proline-rich nuclear receptor coregulatory protein 2 mediates an interaction between mRNA surveillance machinery and decapping complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2008.11.022"}], "href": "https://doi.org/10.1016/j.molcel.2008.11.022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19150429"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19150429"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Tingfeng Lai, Hana Cho, Zhou Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural basis of the PNRC2-mediated link between mrna surveillance and decapping."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Structure (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.str.2012.09.009"}], "href": "https://doi.org/10.1016/j.str.2012.09.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23085078"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23085078"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Pamela Nicholson, Asimina Gkratsou, Christoph Josi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dissecting the functions of SMG5, SMG7, and PNRC2 in nonsense-mediated mRNA decay of human cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "RNA (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1261/rna.063719.117"}], "href": "https://doi.org/10.1261/rna.063719.117"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29348139"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29348139"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Hana Cho, Ok Hyun Park, Joori Park, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Glucocorticoid receptor interacts with PNRC2 in a ligand-dependent manner to recruit UPF1 for rapid mRNA degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1409612112"}], "href": "https://doi.org/10.1073/pnas.1409612112"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25775514"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25775514"}]}]}]}