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

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

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.3390/ijms222212178
Journal or Publication Title: International Journal of Molecular Sciences
Volume: 22
Number: 22
Page Range: p. 12178
Date: 2021
Divisions: Gene and Stem Cell Therapy
Science Support
Depositing User: General Admin
Identification Number: 10.3390/ijms222212178
ISSN: 1422-0067
Date Deposited: 17 Mar 2022 01:34
Abstract:

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.

Creators:
Creators
Email
Dhungel, Bijay P.
UNSPECIFIED
Monteuuis, Geoffray
UNSPECIFIED
Giardina, Caroline
UNSPECIFIED
Tabar, Mehdi S.
UNSPECIFIED
Feng, Yue
UNSPECIFIED
Metierre, Cynthia
UNSPECIFIED
Ho, Sarah
UNSPECIFIED
Nagarajah, Rajini
UNSPECIFIED
Fontaine, Angela R. M.
UNSPECIFIED
Shah, Jaynish S.
UNSPECIFIED
Gokal, Divya
UNSPECIFIED
Bailey, Charles G.
UNSPECIFIED
Schmitz, Ulf
UNSPECIFIED
Rasko, John E. J.
UNSPECIFIED
Last Modified: 17 Mar 2022 01:34
URI: https://eprints.centenary.org.au/id/eprint/1193

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