{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T01:18:07Z","timestamp":1783214287885,"version":"3.54.6"},"update-to":[{"DOI":"10.1371\/journal.pgen.1009985","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,1,3]],"date-time":"2022-01-03T00:00:00Z","timestamp":1641168000000}}],"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T00:00:00Z","timestamp":1639958400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"cprit training grant","award":["RP160283"],"award-info":[{"award-number":["RP160283"]}]},{"DOI":"10.13039\/100000892","name":"prostate cancer foundation","doi-asserted-by":"publisher","award":["2020 Tad Smith & Caroline Fitzgibbons-PCF Young Investigator Award"],"award-info":[{"award-number":["2020 Tad Smith & Caroline Fitzgibbons-PCF Young Investigator Award"]}],"id":[{"id":"10.13039\/100000892","id-type":"DOI","asserted-by":"publisher"}]},{"name":"e&m foundation pre-doctoral fellowship for biomedical research"},{"name":"DOD Idea Development Award","award":["PC190612"],"award-info":[{"award-number":["PC190612"]}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>Oncogenic fusion genes as the result of chromosomal rearrangements are important for understanding genome instability in cancer cells and developing useful cancer therapies. To date, the mechanisms that create such oncogenic fusion genes are poorly understood. Previously we reported an unappreciated RNA-driven mechanism in human prostate cells in which the expression of chimeric RNA induces specified gene fusions in a sequence-dependent manner. One fundamental question yet to be addressed is whether such RNA-driven gene fusion mechanism is generalizable, or rather, a special case restricted to prostate cells. In this report, we demonstrated that the expression of designed chimeric RNAs in human endometrial stromal cells leads to the formation of JAZF1-SUZ12, a cancer fusion gene commonly found in low-grade endometrial stromal sarcomas. The process is specified by the sequence of chimeric RNA involved and inhibited by estrogen or progesterone. Furthermore, it is the antisense rather than sense chimeric RNAs that effectively drive JAZF1-SUZ12 gene fusion. The induced fusion gene is validated both at the RNA and the genomic DNA level. The ability of designed chimeric RNAs to drive and recapitulate the formation of JAZF1-SUZ12 gene fusion in endometrial cells represents another independent case of RNA-driven gene fusion, suggesting that RNA-driven genomic recombination is a permissible mechanism in mammalian cells. The results could have fundamental implications in the role of RNA in genome stability, and provide important insight in early disease mechanisms related to the formation of cancer fusion genes.<\/jats:p>","DOI":"10.1371\/journal.pgen.1009985","type":"journal-article","created":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T19:01:04Z","timestamp":1640026864000},"page":"e1009985","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["RNA-driven JAZF1-SUZ12 gene fusion in human endometrial stromal cells"],"prefix":"10.1371","volume":"17","author":[{"given":"Sachin Kumar","family":"Gupta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3264-2529","authenticated-orcid":true,"given":"Jocelyn Duen-Ya","family":"Jea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2746-414X","authenticated-orcid":true,"given":"Laising","family":"Yen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,12,20]]},"reference":[{"issue":"6","key":"pgen.1009985.ref001","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/nrc3947","article-title":"The emerging complexity of gene fusions in cancer","volume":"15","author":"F Mertens","year":"2015","journal-title":"Nat Rev Cancer"},{"issue":"4","key":"pgen.1009985.ref002","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/nrc2091","article-title":"The impact of translocations and gene fusions on cancer causation","volume":"7","author":"F Mitelman","year":"2007","journal-title":"Nat Rev Cancer"},{"issue":"3","key":"pgen.1009985.ref003","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1002\/gcc.10178","article-title":"Lymphoma- and leukemia-associated chromosomal translocations in healthy individuals","volume":"36","author":"S Janz","year":"2003","journal-title":"Genes Chromosomes Cancer"},{"issue":"4","key":"pgen.1009985.ref004","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1046\/j.1365-2141.1997.4663270.x","article-title":"Incidence of AML1\/ETO fusion transcripts in patients entered into the MRC AML trials. 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