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

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...

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Autores principales:	Bijay P. Dhungel, Geoffray Monteuuis, Caroline Giardina, Mehdi S. Tabar, Yue Feng, Cynthia Metierre, Sarah Ho, Rajini Nagarajah, Angela R. M. Fontaine, Jaynish S. Shah, Divya Gokal, Charles G. Bailey, Ulf Schmitz, John E. J. Rasko
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	chimeric RNAs Fusion RNAs encoding protein fusion transcript linc-223 miR-223 host gene trans-splicing Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/76580557ad97406c8cd6513f7e7d7f09
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spelling	oai:doaj.org-article:76580557ad97406c8cd6513f7e7d7f092021-11-25T17:54:00ZThe Fusion of <i>CLEC12A</i> and <i>MIR223HG</i> Arises from a <i>trans</i>-Splicing Event in Normal and Transformed Human Cells10.3390/ijms2222121781422-00671661-6596https://doaj.org/article/76580557ad97406c8cd6513f7e7d7f092021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12178https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Chimeric 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 <i>CLEC12A-MIR223HG</i>, a novel chimeric transcript produced by the fusion of the cell surface receptor <i>CLEC12A</i> and the <i>miRNA-223</i> host gene (<i>MIR223HG</i>), first identified in chronic myeloid leukemia (CML) patients. Surprisingly, we observed that <i>CLEC12A-MIR223HG</i> is not just expressed in CML, but also in a variety of normal tissues and cell lines. <i>CLEC12A-MIR223HG</i> expression is elevated in pro-monocytic cells resistant to chemotherapy and during monocyte-to-macrophage differentiation. We observed that <i>CLEC12A-MIR223HG</i> is a product of <i>trans</i>-splicing rather than a chromosomal rearrangement and that transcriptional activation of <i>CLEC12A</i> with the CRISPR/Cas9 Synergistic Activation Mediator (SAM) system increases <i>CLEC12A-MIR223HG</i> expression. <i>CLEC12A-MIR223HG</i> 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 <i>CLEC12A-MIR223HG</i> in the regulation of <i>CLEC12A</i> function. Our workflow also serves as a template to study other uncharacterized chimeric RNAs.Bijay P. DhungelGeoffray MonteuuisCaroline GiardinaMehdi S. TabarYue FengCynthia MetierreSarah HoRajini NagarajahAngela R. M. FontaineJaynish S. ShahDivya GokalCharles G. BaileyUlf SchmitzJohn E. J. RaskoMDPI AGarticlechimeric RNAsFusion RNAs encoding proteinfusion transcriptlinc-223miR-223 host genetrans-splicingBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12178, p 12178 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	chimeric RNAs Fusion RNAs encoding protein fusion transcript linc-223 miR-223 host gene trans-splicing Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	chimeric RNAs Fusion RNAs encoding protein fusion transcript linc-223 miR-223 host gene trans-splicing Biology (General) QH301-705.5 Chemistry QD1-999 Bijay P. Dhungel Geoffray Monteuuis Caroline Giardina Mehdi S. Tabar Yue Feng Cynthia Metierre Sarah Ho Rajini Nagarajah Angela R. M. Fontaine Jaynish S. Shah Divya Gokal Charles G. Bailey Ulf Schmitz John E. J. Rasko The Fusion of <i>CLEC12A</i> and <i>MIR223HG</i> Arises from a <i>trans</i>-Splicing Event in Normal and Transformed Human Cells
description	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 <i>CLEC12A-MIR223HG</i>, a novel chimeric transcript produced by the fusion of the cell surface receptor <i>CLEC12A</i> and the <i>miRNA-223</i> host gene (<i>MIR223HG</i>), first identified in chronic myeloid leukemia (CML) patients. Surprisingly, we observed that <i>CLEC12A-MIR223HG</i> is not just expressed in CML, but also in a variety of normal tissues and cell lines. <i>CLEC12A-MIR223HG</i> expression is elevated in pro-monocytic cells resistant to chemotherapy and during monocyte-to-macrophage differentiation. We observed that <i>CLEC12A-MIR223HG</i> is a product of <i>trans</i>-splicing rather than a chromosomal rearrangement and that transcriptional activation of <i>CLEC12A</i> with the CRISPR/Cas9 Synergistic Activation Mediator (SAM) system increases <i>CLEC12A-MIR223HG</i> expression. <i>CLEC12A-MIR223HG</i> 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 <i>CLEC12A-MIR223HG</i> in the regulation of <i>CLEC12A</i> function. Our workflow also serves as a template to study other uncharacterized chimeric RNAs.
format	article
author	Bijay P. Dhungel Geoffray Monteuuis Caroline Giardina Mehdi S. Tabar Yue Feng Cynthia Metierre Sarah Ho Rajini Nagarajah Angela R. M. Fontaine Jaynish S. Shah Divya Gokal Charles G. Bailey Ulf Schmitz John E. J. Rasko
author_facet	Bijay P. Dhungel Geoffray Monteuuis Caroline Giardina Mehdi S. Tabar Yue Feng Cynthia Metierre Sarah Ho Rajini Nagarajah Angela R. M. Fontaine Jaynish S. Shah Divya Gokal Charles G. Bailey Ulf Schmitz John E. J. Rasko
author_sort	Bijay P. Dhungel
title	The Fusion of <i>CLEC12A</i> and <i>MIR223HG</i> Arises from a <i>trans</i>-Splicing Event in Normal and Transformed Human Cells
title_short	The Fusion of <i>CLEC12A</i> and <i>MIR223HG</i> Arises from a <i>trans</i>-Splicing Event in Normal and Transformed Human Cells
title_full	The Fusion of <i>CLEC12A</i> and <i>MIR223HG</i> Arises from a <i>trans</i>-Splicing Event in Normal and Transformed Human Cells
title_fullStr	The Fusion of <i>CLEC12A</i> and <i>MIR223HG</i> Arises from a <i>trans</i>-Splicing Event in Normal and Transformed Human Cells
title_full_unstemmed	The Fusion of <i>CLEC12A</i> and <i>MIR223HG</i> Arises from a <i>trans</i>-Splicing Event in Normal and Transformed Human Cells
title_sort	fusion of <i>clec12a</i> and <i>mir223hg</i> arises from a <i>trans</i>-splicing event in normal and transformed human cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/76580557ad97406c8cd6513f7e7d7f09
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The Fusion of <i>CLEC12A</i> and <i>MIR223HG</i> Arises from a <i>trans</i>-Splicing Event in Normal and Transformed Human Cells

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