{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T19:14:06Z","timestamp":1768418046868,"version":"3.49.0"},"reference-count":53,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T00:00:00Z","timestamp":1636502400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chimeric RNAs are often associated with chromosomal rearrangements in cancer. In addition, they are also widely detected in normal tissues, contributing to transcriptomic complexity. Despite their prevalence, little is known about the characteristics and functions of chimeric RNAs. Here, we examine the genetic structure and biological roles of CLEC12A-MIR223HG, a novel chimeric transcript produced by the fusion of the cell surface receptor CLEC12A and the miRNA-223 host gene (MIR223HG), first identified in chronic myeloid leukemia (CML) patients. Surprisingly, we observed that CLEC12A-MIR223HG is not just expressed in CML, but also in a variety of normal tissues and cell lines. CLEC12A-MIR223HG expression is elevated in pro-monocytic cells resistant to chemotherapy and during monocyte-to-macrophage differentiation. We observed that CLEC12A-MIR223HG is a product of trans-splicing rather than a chromosomal rearrangement and that transcriptional activation of CLEC12A with the CRISPR\/Cas9 Synergistic Activation Mediator (SAM) system increases CLEC12A-MIR223HG expression. CLEC12A-MIR223HG translates into a chimeric protein, which largely resembles CLEC12A but harbours an altered C-type lectin domain altering key disulphide bonds. These alterations result in differences in post-translational modifications, cellular localization, and protein\u2013protein interactions. Taken together, our observations support a possible involvement of CLEC12A-MIR223HG in the regulation of CLEC12A function. Our workflow also serves as a template to study other uncharacterized chimeric RNAs.<\/jats:p>","DOI":"10.3390\/ijms222212178","type":"journal-article","created":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T09:19:21Z","timestamp":1636535961000},"page":"12178","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The Fusion of CLEC12A and MIR223HG Arises from a trans-Splicing Event in Normal and Transformed Human Cells"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5130-5224","authenticated-orcid":false,"given":"Bijay P.","family":"Dhungel","sequence":"first","affiliation":[{"name":"Gene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown, NSW 2050, Australia"},{"name":"Faculty of Medicine & Health, The University of Sydney, Camperdown, NSW 2006, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7193-7771","authenticated-orcid":false,"given":"Geoffray","family":"Monteuuis","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Developmental Biology, University of Helsinki, 00014 Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3681-057X","authenticated-orcid":false,"given":"Caroline","family":"Giardina","sequence":"additional","affiliation":[{"name":"Gene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown, NSW 2050, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehdi S.","family":"Tabar","sequence":"additional","affiliation":[{"name":"Gene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown, NSW 2050, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Feng","sequence":"additional","affiliation":[{"name":"Gene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown, NSW 2050, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cynthia","family":"Metierre","sequence":"additional","affiliation":[{"name":"Gene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown, NSW 2050, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Ho","sequence":"additional","affiliation":[{"name":"Gene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown, NSW 2050, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajini","family":"Nagarajah","sequence":"additional","affiliation":[{"name":"Gene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown, NSW 2050, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela R. M.","family":"Fontaine","sequence":"additional","affiliation":[{"name":"Centenary Imaging and Sydney Cytometry Centenary Institute, The University of Sydney, Camperdown, NSW 2050, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaynish S.","family":"Shah","sequence":"additional","affiliation":[{"name":"Gene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown, NSW 2050, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Divya","family":"Gokal","sequence":"additional","affiliation":[{"name":"Gene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown, NSW 2050, Australia"},{"name":"Faculty of Medicine & Health, The University of Sydney, Camperdown, NSW 2006, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4725-7829","authenticated-orcid":false,"given":"Charles G.","family":"Bailey","sequence":"additional","affiliation":[{"name":"Gene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown, NSW 2050, Australia"},{"name":"Faculty of Medicine & Health, The University of Sydney, Camperdown, NSW 2006, Australia"},{"name":"Cancer & Gene Regulation Laboratory Centenary Institute, The University of Sydney, Camperdown, NSW 2050, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5806-4662","authenticated-orcid":false,"given":"Ulf","family":"Schmitz","sequence":"additional","affiliation":[{"name":"Department of Molecular & Cell Biology, College of Public Health, Medical & Vet Sciences, James Cook University, Townsville, QLD 4811, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2975-807X","authenticated-orcid":false,"given":"John E. J.","family":"Rasko","sequence":"additional","affiliation":[{"name":"Gene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown, NSW 2050, Australia"},{"name":"Faculty of Medicine & Health, The University of Sydney, Camperdown, NSW 2006, Australia"},{"name":"Cell and Molecular Therapies, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.trecan.2016.07.006","article-title":"Intergenically Spliced Chimeric RNAs in Cancer","volume":"2","author":"Jia","year":"2016","journal-title":"Trends Cancer"},{"key":"ref_2","first-page":"139","article-title":"Chromosomal translocations in cancer","volume":"1786","author":"Nambiar","year":"2008","journal-title":"Biochim. Biophys. 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