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The Fusion of CLEC12A and MIR223HG Arises from a trans -Splicing Event in Normal and Transformed Human Cells.

التفاصيل البيبلوغرافية
العنوان: The Fusion of CLEC12A and MIR223HG Arises from a trans -Splicing Event in Normal and Transformed Human Cells.
المؤلفون: Dhungel BP; Gene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown, NSW 2050, Australia.; Faculty of Medicine & Health, The University of Sydney, Camperdown, NSW 2006, Australia., Monteuuis G; Department of Biochemistry and Developmental Biology, University of Helsinki, 00014 Helsinki, Finland., Giardina C; Gene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown, NSW 2050, Australia., Tabar MS; Gene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown, NSW 2050, Australia., Feng Y; Gene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown, NSW 2050, Australia., Metierre C; Gene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown, NSW 2050, Australia., Ho S; Gene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown, NSW 2050, Australia., Nagarajah R; Gene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown, NSW 2050, Australia., Fontaine ARM; Centenary Imaging and Sydney Cytometry Centenary Institute, The University of Sydney, Camperdown, NSW 2050, Australia., Shah JS; Gene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown, NSW 2050, Australia., Gokal D; Gene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown, NSW 2050, Australia.; Faculty of Medicine & Health, The University of Sydney, Camperdown, NSW 2006, Australia., Bailey CG; Gene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown, NSW 2050, Australia.; Faculty of Medicine & Health, The University of Sydney, Camperdown, NSW 2006, Australia.; Cancer & Gene Regulation Laboratory Centenary Institute, The University of Sydney, Camperdown, NSW 2050, Australia., Schmitz U; Department of Molecular & Cell Biology, College of Public Health, Medical & Vet Sciences, James Cook University, Townsville, QLD 4811, Australia., Rasko JEJ; Gene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown, NSW 2050, Australia.; Faculty of Medicine & Health, The University of Sydney, Camperdown, NSW 2006, Australia.; Cell and Molecular Therapies, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia.
المصدر: International journal of molecular sciences [Int J Mol Sci] 2021 Nov 10; Vol. 22 (22). Date of Electronic Publication: 2021 Nov 10.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, [2000-
مواضيع طبية MeSH: Gene Fusion* , Trans-Splicing*, Lectins, C-Type/*genetics , Leukemia, Myeloid/*genetics , MicroRNAs/*genetics , Mutant Chimeric Proteins/*genetics , Receptors, Mitogen/*genetics, Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Cell Differentiation/genetics ; Cell Line ; Cytarabine/pharmacology ; Humans ; Lectins, C-Type/metabolism ; Leukemia, Myeloid/metabolism ; MicroRNAs/metabolism ; Mutant Chimeric Proteins/metabolism ; Receptors, Mitogen/metabolism ; Transcriptional Activation
مستخلص: 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-protein 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.
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فهرسة مساهمة: Keywords: C-type lectin; CCL1; Fusion RNAs encoding protein; alternative splicing; chimeric RNAs; chronic myeloid leukemia; fusion transcript; linc-223; miR-223 host gene; myeloid cell differentiation; trans-splicing
المشرفين على المادة: 0 (Antineoplastic Agents)
0 (CLEC12A protein, human)
0 (Lectins, C-Type)
0 (MIRN223 microRNA, human)
0 (MicroRNAs)
0 (Mutant Chimeric Proteins)
0 (Receptors, Mitogen)
04079A1RDZ (Cytarabine)
تواريخ الأحداث: Date Created: 20211127 Date Completed: 20220119 Latest Revision: 20220119
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC8625150
DOI: 10.3390/ijms222212178
PMID: 34830054
قاعدة البيانات: MEDLINE
الوصف
تدمد:1422-0067
DOI:10.3390/ijms222212178