{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:09:03Z","timestamp":1789776543500,"version":"4.0.1"},"reference-count":128,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T00:00:00Z","timestamp":1655942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01 CA251753-01"],"award-info":[{"award-number":["R01 CA251753-01"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","award":["RSG-20-060-01-RMC"],"award-info":[{"award-number":["RSG-20-060-01-RMC"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","award":["RSG-21-066-01-CCG"],"award-info":[{"award-number":["RSG-21-066-01-CCG"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"BBSRC","doi-asserted-by":"publisher","award":["BB\/K009393\/1"],"award-info":[{"award-number":["BB\/K009393\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Royal Society Wolfson","award":["WM170036"],"award-info":[{"award-number":["WM170036"]}]},{"name":"CNPq Science","award":["245392\/2012-2"],"award-info":[{"award-number":["245392\/2012-2"]}]},{"DOI":"10.13039\/100000054","name":"NCI","doi-asserted-by":"publisher","award":["P30 CA016058"],"award-info":[{"award-number":["P30 CA016058"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>DICER1 syndrome is a cancer pre-disposition disorder caused by mutations that disrupt the function of DICER1 in miRNA processing. Studying the molecular, cellular and oncogenic effects of these mutations can reveal novel mechanisms that control cell homeostasis and tumor biology. Here, we conduct the first analysis of pathogenic DICER1 syndrome allele from the DICER1 3\u2032UTR. We find that the DICER1 syndrome allele, rs1252940486, abolishes interaction with the PUMILIO RNA binding protein with the DICER1 3\u2032UTR, resulting in the degradation of the DICER1 mRNA by AUF1. This single mutational event leads to diminished DICER1 mRNA and protein levels, and widespread reprogramming of miRNA networks. The in-depth characterization of the rs1252940486 DICER1 allele, reveals important post-transcriptional regulatory events that control DICER1 levels.<\/jats:p>","DOI":"10.1093\/nar\/gkac499","type":"journal-article","created":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T13:07:15Z","timestamp":1655989635000},"page":"7048-7066","source":"Crossref","is-referenced-by-count":11,"title":["PUMILIO competes with AUF1 to control DICER1 RNA levels and miRNA processing"],"prefix":"10.1093","volume":"50","author":[{"given":"Swetha","family":"Rajasekaran","sequence":"first","affiliation":[{"name":"Department of Cancer Biology and Genetics, The Ohio State University , 460 West 12th Avenue , Columbus , OH 43210 , USA"},{"name":"The Ohio State University Comprehensive Cancer Center, The Ohio State University , 460 West 12th Avenue , Columbus , OH 43210 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eshan","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology and Genetics, The Ohio State University , 460 West 12th Avenue , Columbus , OH 43210 , USA"},{"name":"The Ohio State University Comprehensive Cancer Center, The Ohio State University , 460 West 12th Avenue , Columbus , OH 43210 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel R","family":"Ching","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Massachusetts General Hospital , Boston , MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misbah","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology and Genetics, The Ohio State University , 460 West 12th Avenue , Columbus , OH 43210 , USA"},{"name":"The Ohio State University Comprehensive Cancer Center, The Ohio State University , 460 West 12th Avenue , Columbus , OH 43210 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jalal\u00a0K","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology and Genetics, The Ohio State University , 460 West 12th Avenue , Columbus , OH 43210 , USA"},{"name":"The Ohio State University Comprehensive Cancer Center, The Ohio State University , 460 West 12th Avenue , Columbus , OH 43210 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela F","family":"Gradia","sequence":"additional","affiliation":[{"name":"Department of Microbial Sciences, School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey , Guildford , Surrey GU2 7XH, UK"},{"name":"Department of Genetics, Federal University of Parana , Curitiba , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7306-912X","authenticated-orcid":false,"given":"Chenyu","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology and Genetics, The Ohio State University , 460 West 12th Avenue , Columbus , OH 43210 , USA"},{"name":"The Ohio State University Comprehensive Cancer Center, The Ohio State University , 460 West 12th Avenue , Columbus , OH 43210 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie J","family":"Bouley","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Massachusetts General Hospital , Boston , MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dayna\u00a0L","family":"Mercadante","sequence":"additional","affiliation":[{"name":"Bioinformatics and Computational Biology Program, Worcester Polytechnic Institute, 100 Institute Road , Worcester , MA 01609, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amity L","family":"Manning","sequence":"additional","affiliation":[{"name":"Bioinformatics and Computational Biology Program, Worcester Polytechnic Institute, 100 Institute Road , Worcester , MA 01609, USA"},{"name":"Department of Biology and Biotechnology, Worcester Polytechnic Institute, 100 Institute Road , Worcester , MA 01609, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2398-6592","authenticated-orcid":false,"given":"Andr\u00e9 P","family":"Gerber","sequence":"additional","affiliation":[{"name":"Department of Microbial Sciences, School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey , Guildford , Surrey GU2 7XH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James\u00a0A","family":"Walker","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Massachusetts General Hospital , Boston , MA 02114, USA"},{"name":"Department of Neurology, Massachusetts General Hospital, Harvard Medical School , Boston , USA"},{"name":"Cancer Program, Broad Institute of MIT and Harvard , Cambridge , MA 02142, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2054-5206","authenticated-orcid":false,"given":"Wayne\u00a0O","family":"Miles","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology and Genetics, The Ohio State University , 460 West 12th Avenue , Columbus , OH 43210 , USA"},{"name":"The Ohio State University Comprehensive Cancer Center, The Ohio State University , 460 West 12th Avenue , Columbus , OH 43210 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,6,23]]},"reference":[{"key":"2022070723570149400_B1","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/35053110","article-title":"Role for a bidentate ribonuclease in 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Top. Microbiol. Immunol."},{"key":"2022070723570149400_B3","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1261\/rna.7272305","article-title":"The contributions of dsRNA structure to dicer specificity and efficiency","volume":"11","author":"Vermeulen","year":"2005","journal-title":"RNA"},{"key":"2022070723570149400_B4","doi-asserted-by":"crossref","first-page":"2979","DOI":"10.1101\/gad.1384005","article-title":"A human, ATP-independent, RISC assembly machine fueled by pre-miRNA","volume":"19","author":"Maniataki","year":"2005","journal-title":"Genes Dev."},{"key":"2022070723570149400_B5","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1126\/science.1121638","article-title":"Structural basis for double-stranded RNA processing by dicer","volume":"311","author":"MacRae","year":"2006","journal-title":"Science"},{"key":"2022070723570149400_B6","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1038\/ng1611","article-title":"Short double-stranded RNA induces transcriptional gene silencing in human cancer cells in the absence of DNA methylation","volume":"37","author":"Ting","year":"2005","journal-title":"Nat. Genet."},{"key":"2022070723570149400_B7","doi-asserted-by":"crossref","first-page":"4640","DOI":"10.1093\/nar\/gkt1413","article-title":"Interplay between pre-mRNA splicing and microRNA biogenesis within the supraspliceosome","volume":"42","author":"Agranat-Tamir","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"2022070723570149400_B8","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1101\/gr.082701.108","article-title":"Most mammalian mRNAs are conserved targets of microRNAs","volume":"19","author":"Friedman","year":"2008","journal-title":"Genome Res."},{"key":"2022070723570149400_B9","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/nrm2085","article-title":"Illuminating the silence: understanding the structure and function of small RNAs","volume":"8","author":"Rana","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2022070723570149400_B10","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.devcel.2006.09.009","article-title":"The diverse functions of micrornas in animal development and disease","volume":"11","author":"Kloosterman","year":"2006","journal-title":"Dev. Cell"},{"key":"2022070723570149400_B11","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/35005107","article-title":"An RNA-directed nuclease mediates post-transcriptional gene silencing in drosophila cells","volume":"404","author":"Hammond","year":"2000","journal-title":"Nature"},{"key":"2022070723570149400_B12","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/s41580-018-0045-7","article-title":"Regulation of microRNA function in animals","volume":"20","author":"Gebert","year":"2019","journal-title":"Nat. Rev. Mol. 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Natl. Acad. Sci. U.S.A."},{"key":"2022070723570149400_B22","doi-asserted-by":"crossref","first-page":"15524","DOI":"10.1073\/pnas.242606799","article-title":"Nonlinear partial differential equations and applications: frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia","volume":"99","author":"Calin","year":"2002","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2022070723570149400_B23","doi-asserted-by":"crossref","first-page":"13944","DOI":"10.1073\/pnas.0506654102","article-title":"miR-15 and miR-16 induce apoptosis by targeting BCL2","volume":"102","author":"Cimmino","year":"2005","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2022070723570149400_B24","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1056\/NEJMoa050995","article-title":"A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia","volume":"353","author":"Calin","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"2022070723570149400_B25","first-page":"882","article-title":"Reduced accumulation of specific microRNAs in colorectal neoplasia","volume":"1","author":"Michael","year":"2003","journal-title":"Mol. Cancer Res."},{"key":"2022070723570149400_B26","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.cell.2005.01.014","article-title":"RAS is regulated by the let-7 MicroRNA family","volume":"120","author":"Johnson","year":"2005","journal-title":"Cell"},{"key":"2022070723570149400_B27","doi-asserted-by":"crossref","first-page":"5228","DOI":"10.1038\/s41467-018-07657-1","article-title":"Pan-cancer characterisation of microRNA across cancer hallmarks reveals microRNA-mediated downregulation of tumour suppressors","volume":"9","author":"Dhawan","year":"2018","journal-title":"Nat. Commun."},{"key":"2022070723570149400_B28","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/ng1253","article-title":"Dicer is essential for mouse development","volume":"35","author":"Bernstein","year":"2003","journal-title":"Nat. Genet."},{"key":"2022070723570149400_B29","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ejmg.2018.04.011","article-title":"Identification of two 14q32 deletions involving DICER1 associated with the development of DICER1-related tumors","volume":"62","author":"Herriges","year":"2019","journal-title":"Eur. J. Med. Genet."},{"key":"2022070723570149400_B30","doi-asserted-by":"crossref","first-page":"e29166","DOI":"10.1371\/journal.pone.0029166","article-title":"Beta-Cell specific deletion of dicer1 leads to defective insulin secretion and diabetes mellitus","volume":"6","author":"Kalis","year":"2011","journal-title":"PLoS One"},{"key":"2022070723570149400_B31","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1101\/gad.1248505","article-title":"Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing","volume":"19","author":"Kanellopoulou","year":"2005","journal-title":"Genes Dev."},{"key":"2022070723570149400_B32","doi-asserted-by":"crossref","first-page":"C285","DOI":"10.1152\/ajpcell.00278.2018","article-title":"An inducible knockout of dicer in adult mice does not affect endurance exercise-induced muscle adaptation","volume":"316","author":"Oikawa","year":"2019","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"2022070723570149400_B33","doi-asserted-by":"crossref","first-page":"e44060","DOI":"10.1371\/journal.pone.0044060","article-title":"Gene network and pathway analysis of mice with conditional ablation of dicer in post-mitotic neurons","volume":"7","author":"Dorval","year":"2012","journal-title":"PLoS One"},{"key":"2022070723570149400_B34","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.stemcr.2018.07.013","article-title":"DICER1 is essential for self-renewal of human embryonic stem cells","volume":"11","author":"Teijeiro","year":"2018","journal-title":"Stem Cell Rep."},{"key":"2022070723570149400_B35","doi-asserted-by":"crossref","first-page":"3099","DOI":"10.1038\/onc.2013.281","article-title":"A dosage-dependent pleiotropic role of dicer in prostate cancer growth and metastasis","volume":"33","author":"Zhang","year":"2013","journal-title":"Oncogene"},{"key":"2022070723570149400_B36","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1111\/j.1349-7006.2005.00015.x","article-title":"Reduced expression of dicer associated with poor prognosis in lung cancer patients","volume":"96","author":"Karube","year":"2005","journal-title":"Cancer Sci."},{"key":"2022070723570149400_B37","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.prp.2012.05.001","article-title":"Immunohistochemical study of dicer and drosha expression in the benign and malignant lesions of gallbladder and their clinicopathological significances","volume":"208","author":"Shu","year":"2012","journal-title":"Pathology - Res. Pract."},{"key":"2022070723570149400_B38","doi-asserted-by":"crossref","first-page":"4003","DOI":"10.1038\/onc.2013.398","article-title":"Impaired DICER1 function promotes stemness and metastasis in colon cancer","volume":"33","author":"Iliou","year":"2014","journal-title":"Oncogene"},{"key":"2022070723570149400_B39","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1002\/path.2658","article-title":"Prognostic significance of dicer expression in ovarian cancer-link to global microRNA changes and oestrogen receptor expression","volume":"220","author":"Faggad","year":"2010","journal-title":"J. Pathol."},{"key":"2022070723570149400_B40","doi-asserted-by":"crossref","first-page":"e83724","DOI":"10.1371\/journal.pone.0083724","article-title":"Prognostic significance of deregulated dicer expression in breast cancer","volume":"8","author":"Caffrey","year":"2013","journal-title":"PLoS One"},{"key":"2022070723570149400_B41","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.2353\/ajpath.2006.060480","article-title":"Up-regulation of dicer, a component of the MicroRNA machinery, in prostate adenocarcinoma","volume":"169","author":"Chiosea","year":"2006","journal-title":"Am. J. Pathol."},{"key":"2022070723570149400_B42","doi-asserted-by":"crossref","first-page":"7322","DOI":"10.1158\/1078-0432.CCR-06-0515","article-title":"RNASEN regulates cell proliferation and affects survival in esophageal cancer patients","volume":"12","author":"Sugito","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"2022070723570149400_B43","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1016\/j.ejca.2011.01.006","article-title":"Overexpression of dicer predicts poor survival in colorectal cancer","volume":"47","author":"Faber","year":"2011","journal-title":"Eur. J. Cancer"},{"key":"2022070723570149400_B44","doi-asserted-by":"crossref","first-page":"72672","DOI":"10.18632\/oncotarget.12183","article-title":"Role of dicer as a prognostic predictor for survival in cancer patients: a systematic review with a meta-analysis","volume":"7","author":"Shan","year":"2016","journal-title":"Oncotarget"},{"key":"2022070723570149400_B45","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1200\/JCO.2018.78.4678","article-title":"Neoplasm risk among individuals with a pathogenic germline variant in DICER1","volume":"37","author":"Stewart","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"2022070723570149400_B46","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1126\/science.1174334","article-title":"DICER1 mutations in familial pleuropulmonary blastoma","volume":"325","author":"Hill","year":"2009","journal-title":"Science"},{"key":"2022070723570149400_B47","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/S0022-3476(96)70393-1","article-title":"Pleuropulmonary blastoma: a marker for familial disease","volume":"128","author":"JR","year":"1996","journal-title":"J. Pediatr."},{"key":"2022070723570149400_B48","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1210\/clinem\/dgab025","article-title":"Prevalence and spectrum of DICER1 mutations in Adult-onset thyroid nodules with indeterminate cytology","volume":"106","author":"Chong","year":"2021","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2022070723570149400_B49","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.epsc.2016.05.014","article-title":"DICER1 syndrome and thyroid disease","volume":"11","author":"Canfarotta","year":"2016","journal-title":"J. Pediatr. Surg. Case Rep."},{"key":"2022070723570149400_B50","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1158\/1078-0432.CCR-17-3089","article-title":"Dicer1 and associated conditions: identification of at-risk individuals and recommended surveillance strategies","volume":"24","author":"Schultz","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"2022070723570149400_B51","doi-asserted-by":"crossref","first-page":"4802","DOI":"10.1038\/ncomms5802","article-title":"Somatic mutations in DROSHA and DICER1 impair microRNA biogenesis through distinct mechanisms in wilms tumours","volume":"5","author":"Rakheja","year":"2014","journal-title":"Nat. Commun."},{"key":"2022070723570149400_B52","doi-asserted-by":"crossref","first-page":"E555","DOI":"10.1002\/mgg3.555","article-title":"The prevalence of germline DICER1 pathogenic variation in cancer populations","volume":"7","author":"Kim","year":"2019","journal-title":"Mol. Genet. Genomic Med."},{"key":"2022070723570149400_B53","doi-asserted-by":"crossref","first-page":"214","DOI":"10.12688\/f1000research.6746.2","article-title":"Temporal order of RNase IIIb and loss-of-function mutations during development determines phenotype in pleuropulmonary blastoma \/DICER1 syndrome: a unique variant of the two-hit tumor suppression model","volume":"4","author":"Brenneman","year":"2018","journal-title":"F1000Research"},{"key":"2022070723570149400_B54","doi-asserted-by":"crossref","first-page":"a034728","DOI":"10.1101\/cshperspect.a034728","article-title":"What are 3\u2032 UTRs doing?","volume":"11","author":"Mayr","year":"2019","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"2022070723570149400_B55","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1146\/annurev-genet-120116-024704","article-title":"Regulation by 3\u2032-untranslated regions","volume":"51","author":"Mayr","year":"2017","journal-title":"Annu. Rev. Genet."},{"key":"2022070723570149400_B56","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1007\/s11033-019-05142-6","article-title":"Functions, mechanisms and regulation of pumilio\/puf family RNA binding proteins: a comprehensive review","volume":"47","author":"Nishanth","year":"2020","journal-title":"Mol. Biol. 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