{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRNase L is a 2′–5′ oligoadenylate–dependent endoribonuclease central to the interferon‐mediated antiviral response. Upon binding to 2–5A molecules—produced by double‐stranded RNA–activated oligoadenylate synthetases—it dimerizes into a crossed homodimer whose ankyrin repeat and kinase homology domains mediate ligand binding and sequence‐specific RNA cleavage. In doing so, RNase L degrades viral transcripts as well as selected cellular RNAs (including rRNAs, tRNAs, and Y‐RNAs) to rapidly shut down protein synthesis and amplify antiviral signaling. In addition, viral countermeasures such as the influenza NS1 protein’s sequestration of dsRNA, as well as viral phosphodiesterases that degrade 2–5A, underscore the critical role of RNase L in antiviral defense."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its antiviral functions, RNase L regulates diverse aspects of cellular homeostasis. It interfaces with key regulatory proteins—including the translation termination factor eRF3, the RNA–binding protein HuR, the scaffolding protein IQGAP1, and innate receptors such as NOD2—to modulate mRNA stability, translation fidelity, and stress kinase signaling (e.g., activation of JNK). The generation of small dsRNA fragments by RNase L further engages signaling cascades that influence the balance between autophagy and apoptosis, and modulate cellular motility and metastatic potential."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEpidemiologic and genetic studies have implicated RNASEL as a candidate tumor suppressor, with specific germline and somatic variants correlating with increased risk and aggressive forms of prostate, pancreatic, colorectal, and other cancers. Several variants—such as those leading to reduced catalytic activity—have been associated with earlier disease onset, enhanced inflammatory cytokine production, and altered responses to hormonal signals. Collectively, these findings underscore a dual role for RNase L in antiviral immunity and in the modulation of cancer predisposition, highlighting its potential as both a biomarker and a therapeutic target."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "21", "end_ref": "39"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ji-Young Min, Robert M Krug "}, {"type": "b", "children": [{"type": "t", "text": "The primary function of RNA binding by the influenza A virus NS1 protein in infected cells: Inhibiting the 2'-5' oligo (A) synthetase/RNase L pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0602184103"}], "href": "https://doi.org/10.1073/pnas.0602184103"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16627618"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16627618"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yuchen Han, Gena Whitney, Jesse Donovan, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Interaction between the androgen receptor and RNase L mediates a cross-talk between the interferon and androgen signaling pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.C500324200"}], "href": "https://doi.org/10.1074/jbc.C500324200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16166078"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16166078"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "W Al-Ahmadi, L Al-Haj, F A Al-Mohanna, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RNase L downmodulation of the RNA-binding protein, HuR, and cellular growth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2009.16"}], "href": "https://doi.org/10.1038/onc.2009.16"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19252527"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19252527"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Jae W Dugan, Amador Albor, Larry David, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Regulation of human RNase-L by the miR-29 family reveals a novel oncogenic role in chronic myelogenous leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Interferon Cytokine Res (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/jir.2012.0062"}], "href": "https://doi.org/10.1089/jir.2012.0062"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23113544"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23113544"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Mohammad Adnan Siddiqui, Sushovita Mukherjee, Praveen Manivannan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RNase L Cleavage Products Promote Switch from Autophagy to Apoptosis by Caspase-Mediated Cleavage of Beclin-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms160817611"}], "href": "https://doi.org/10.3390/ijms160817611"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26263979"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26263979"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Shuvojit Banerjee, Geqiang Li, Yize Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RNase L is a negative regulator of cell migration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.6246"}], "href": "https://doi.org/10.18632/oncotarget.6246"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26517238"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26517238"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Sneha Rath, Jesse Donovan, Gena Whitney, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human RNase L tunes gene expression by selectively destabilizing the microRNA-regulated transcriptome."}]}, {"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.1513034112"}], "href": "https://doi.org/10.1073/pnas.1513034112"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26668391"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26668391"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Annika Rökman, Tarja Ikonen, Eija H Seppälä, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Germline alterations of the RNASEL gene, a candidate HPC1 gene at 1q25, in patients and families with prostate cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/340450"}], "href": "https://doi.org/10.1086/340450"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11941539"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11941539"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Graham Casey, Phillippa J Neville, Sarah J Plummer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RNASEL Arg462Gln variant is implicated in up to 13% of prostate cancer cases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng1021"}], "href": "https://doi.org/10.1038/ng1021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12415269"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12415269"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Robert H Silverman "}, {"type": "b", "children": [{"type": "t", "text": "Implications for RNase L in prostate cancer biology."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/bi027147i"}], "href": "https://doi.org/10.1021/bi027147i"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12590567"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12590567"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "H Nakazato, K Suzuki, H Matsui, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of genetic polymorphisms of the RNASEL gene on familial prostate cancer risk in a Japanese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Cancer (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.bjc.6601075"}], "href": "https://doi.org/10.1038/sj.bjc.6601075"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12915880"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12915880"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "C Maier, J Haeusler, K Herkommer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutation screening and association study of RNASEL as a prostate cancer susceptibility gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Cancer (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.bjc.6602401"}], "href": "https://doi.org/10.1038/sj.bjc.6602401"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15714208"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15714208"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Detlef K Bartsch, Volker Fendrich, Emily P Slater, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RNASEL germline variants are associated with pancreatic cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cancer (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ijc.21254"}], "href": "https://doi.org/10.1002/ijc.21254"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15981205"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15981205"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Ferrin C Noonan-Wheeler, William Wu, Kimberly A Roehl, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of hereditary prostate cancer gene polymorphic variants with sporadic aggressive prostate carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Prostate (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/pros.20320"}], "href": "https://doi.org/10.1002/pros.20320"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16114055"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16114055"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Imtiaz Yakub, Kristy M Lillibridge, Ana Moran, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Single nucleotide polymorphisms in genes for 2'-5'-oligoadenylate synthetase and RNase L inpatients hospitalized with West Nile virus infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Infect Dis (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/497340"}], "href": "https://doi.org/10.1086/497340"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16235172"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16235172"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Huihua Li, Bee Choo Tai "}, {"type": "b", "children": [{"type": "t", "text": "RNASEL gene polymorphisms and the risk of prostate cancer: a meta-analysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-05-2799"}], "href": "https://doi.org/10.1158/1078-0432.CCR-05-2799"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17020975"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17020975"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Catherine Bisbal, Robert H Silverman "}, {"type": "b", "children": [{"type": "t", "text": "Diverse functions of RNase L and implications in pathology."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochimie (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biochi.2007.02.006"}], "href": "https://doi.org/10.1016/j.biochi.2007.02.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17400356"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17400356"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Stacie J Shook, Joke Beuten, Kathleen C Torkko, et al. 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