{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nWDR12 is a WD40 repeat‐containing protein that plays an essential role in ribosome biogenesis. As a core component of the PeBoW complex together with Pes1 and Bop1, WDR12 is critical for the processing of the 32S ribosomal RNA precursor into mature 5.8S and 28S rRNAs, a fundamental step for ribosome assembly and cell proliferation. Interference with WDR12 function—either by expression of a dominant-negative mutant or an imbalance in complex formation—leads to impaired rRNA processing, accumulation of p53 independently of p19ARF, and a consequent reversible cell cycle arrest. This function has been elucidated through studies demonstrating that recombinant expression of the PeBoW components is sufficient for complex assembly and that the stability of WDR12 is markedly enhanced upon incorporation into this complex."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in ribosome maturation, aberrant expression of WDR12 has been implicated in tumor biology. For example, in glioblastoma, high levels of WDR12 expression correlate with reduced overall and disease-free survival, and its knockdown promotes apoptosis while inhibiting cell proliferation by impeding progression through the cell cycle. These observations support the notion that WDR12 contributes to the malignant behavior of tumor cells and may represent a novel prognostic biomarker and therapeutic target in cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in cell growth and ribosome biogenesis, genetic variants near the WDR12 locus have been associated with an increased risk for myocardial infarction and coronary artery disease, although its cardiac function remains incompletely defined. Recent mechanistic insights have provided further context by revealing that non-coding RNAs—such as circMIRIAF acting as a sponge for miR-544—can modulate WDR12 expression. The enhanced WDR12 expression, in turn, activates downstream signaling pathways including Notch1, thereby exacerbating oxidative stress, inflammation, and myocardial ischemia-reperfusion injury. These findings underscore a multifaceted role for WDR12 in both cardiovascular pathology and cell proliferation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Michael Hölzel, Michaela Rohrmoser, Martin Schlee, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Interdependence of Pes1, Bop1, and WDR12 controls nucleolar localization and assembly of the PeBoW complex required for maturation of the 60S ribosomal subunit."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00172-07"}], "href": "https://doi.org/10.1128/MCB.00172-07"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17353269"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17353269"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Markus Kellner, Michaela Rohrmoser, Ignasi Forné, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DEAD-box helicase DDX27 regulates 3' end formation of ribosomal 47S RNA and stably associates with the PeBoW-complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2015.03.017"}], "href": "https://doi.org/10.1016/j.yexcr.2015.03.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25825154"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25825154"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jun-Liang Li, Cheng Chen, Wei Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Integrative genomic analyses identify WDR12 as a novel oncogene involved in glioblastoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.29635"}], "href": "https://doi.org/10.1002/jcp.29635"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32180229"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32180229"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Sekar Kathiresan, Benjamin F Voight, Shaun Purcell, et al. 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