Intragenic antagonistic roles of protein and circRNA in tumorigenesis
circRNAs arise from back splicing events during mRNA processing, and when deregulated can play an active role in cancer. Here we characterize a new circRNA (circPOK) encoded by the Zbtb7a gene (also kown as POKEMON , LRF ) in the context of mesenchymal tumor progression. circPOK functions as a non-c...
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| Published in | Cell research Vol. 29; no. 8; pp. 628 - 640 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
Nature Publishing Group UK
01.08.2019
Nature Publishing Group |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1001-0602 1748-7838 1748-7838 |
| DOI | 10.1038/s41422-019-0192-1 |
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| Abstract | circRNAs arise from back splicing events during mRNA processing, and when deregulated can play an active role in cancer. Here we characterize a new circRNA (circPOK) encoded by the
Zbtb7a
gene (also kown as
POKEMON
,
LRF
) in the context of mesenchymal tumor progression. circPOK functions as a non-coding proto-oncogenic RNA independently and antithetically to its linear transcript counterpart, which acts as a tumor suppressor by encoding the Pokemon transcription factor. We find that circPOK regulates pro-proliferative and pro-angiogenic factors by co-activation of the ILF2/3 complex. Importantly, the expression of Pokemon protein and circRNA is aberrantly uncoupled in cancer through differential post-transcriptional regulation. Thus, we identify a novel type of genetic unit, the iRegulon, that yields biochemically distinct RNA products, circular and linear, with diverse and antithetical functions. Our findings further expand the cellular repertoire towards the control of normal biological outputs, while aberrant expression of such components may underlie disease pathogenesis including cancer. |
|---|---|
| AbstractList | circRNAs arise from back splicing events during mRNA processing, and when deregulated can play an active role in cancer. Here we characterize a new circRNA (circPOK) encoded by the
Zbtb7a
gene (also kown as
POKEMON
,
LRF
) in the context of mesenchymal tumor progression. circPOK functions as a non-coding proto-oncogenic RNA independently and antithetically to its linear transcript counterpart, which acts as a tumor suppressor by encoding the Pokemon transcription factor. We find that circPOK regulates pro-proliferative and pro-angiogenic factors by co-activation of the ILF2/3 complex. Importantly, the expression of Pokemon protein and circRNA is aberrantly uncoupled in cancer through differential post-transcriptional regulation. Thus, we identify a novel type of genetic unit, the iRegulon, that yields biochemically distinct RNA products, circular and linear, with diverse and antithetical functions. Our findings further expand the cellular repertoire towards the control of normal biological outputs, while aberrant expression of such components may underlie disease pathogenesis including cancer. circRNAs arise from back splicing events during mRNA processing, and when deregulated can play an active role in cancer. Here we characterize a new circRNA (circPOK) encoded by the Zbtb7a gene (also kown as POKEMON, LRF) in the context of mesenchymal tumor progression. circPOK functions as a non-coding proto-oncogenic RNA independently and antithetically to its linear transcript counterpart, which acts as a tumor suppressor by encoding the Pokemon transcription factor. We find that circPOK regulates pro-proliferative and pro-angiogenic factors by co-activation of the ILF2/3 complex. Importantly, the expression of Pokemon protein and circRNA is aberrantly uncoupled in cancer through differential post-transcriptional regulation. Thus, we identify a novel type of genetic unit, the iRegulon, that yields biochemically distinct RNA products, circular and linear, with diverse and antithetical functions. Our findings further expand the cellular repertoire towards the control of normal biological outputs, while aberrant expression of such components may underlie disease pathogenesis including cancer. circRNAs arise from back splicing events during mRNA processing, and when deregulated can play an active role in cancer. Here we characterize a new circRNA (circPOK) encoded by the Zbtb7a gene (also kown as POKEMON, LRF) in the context of mesenchymal tumor progression. circPOK functions as a non-coding proto-oncogenic RNA independently and antithetically to its linear transcript counterpart, which acts as a tumor suppressor by encoding the Pokemon transcription factor. We find that circPOK regulates pro-proliferative and pro-angiogenic factors by co-activation of the ILF2/3 complex. Importantly, the expression of Pokemon protein and circRNA is aberrantly uncoupled in cancer through differential post-transcriptional regulation. Thus, we identify a novel type of genetic unit, the iRegulon, that yields biochemically distinct RNA products, circular and linear, with diverse and antithetical functions. Our findings further expand the cellular repertoire towards the control of normal biological outputs, while aberrant expression of such components may underlie disease pathogenesis including cancer.circRNAs arise from back splicing events during mRNA processing, and when deregulated can play an active role in cancer. Here we characterize a new circRNA (circPOK) encoded by the Zbtb7a gene (also kown as POKEMON, LRF) in the context of mesenchymal tumor progression. circPOK functions as a non-coding proto-oncogenic RNA independently and antithetically to its linear transcript counterpart, which acts as a tumor suppressor by encoding the Pokemon transcription factor. We find that circPOK regulates pro-proliferative and pro-angiogenic factors by co-activation of the ILF2/3 complex. Importantly, the expression of Pokemon protein and circRNA is aberrantly uncoupled in cancer through differential post-transcriptional regulation. Thus, we identify a novel type of genetic unit, the iRegulon, that yields biochemically distinct RNA products, circular and linear, with diverse and antithetical functions. Our findings further expand the cellular repertoire towards the control of normal biological outputs, while aberrant expression of such components may underlie disease pathogenesis including cancer. |
| Author | Deshpande, Vikram Garbutt, Cassandra Dimitrios, Spentzos Loretelli, Cristian Cordon-Cardo, Carlos Castillo-Martin, Mireia Kauppinen, Sakari Nielsen, Gunnlaugur Petur Pandolfi, Pier Paolo Clohessy, John G. Batish, Mona Petri, Andreas Guarnerio, Jlenia Panella, Riccardo Zhang, Yang Mae Katon, Jesse Cheloni, Giulia Simpson, Mark Papa, Antonella Matsumoto, Akinobu |
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| Snippet | circRNAs arise from back splicing events during mRNA processing, and when deregulated can play an active role in cancer. Here we characterize a new circRNA... |
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| SubjectTerms | 14/32 38 38/77 631/67/327 631/67/68 64/60 96/31 Alternative Splicing - genetics Angiogenesis Animals Biomedical and Life Sciences Cancer Carcinogenesis - genetics Cell Biology Cell Line, Tumor Deregulation DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Exons Gene Expression Regulation, Neoplastic Gene Knockout Techniques Gene regulation HEK293 Cells Humans Life Sciences Mesenchymal Stem Cells - metabolism Mesenchyme Mice Mice, Inbred C57BL Mice, Knockout mRNA processing Non-coding RNA Pathogenesis Post-transcription Proteins Proto-Oncogenes - genetics Ribonucleic acid RNA RNA, Circular - genetics RNA, Small Interfering - genetics Sarcoma - genetics Sarcoma - pathology Splicing Transcription Factors - genetics Transcription Factors - metabolism Transfection Tumor suppressor genes Tumorigenesis Tumors |
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| Title | Intragenic antagonistic roles of protein and circRNA in tumorigenesis |
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