| ID | 58103 |
| FullText URL | |
| Author |
Yamamoto, Takahiro
Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University
ORCID
Kaken ID
researchmap
Fujimura, Atsushi
Neutron Therapy Research Center, Okayama University
Wei, Fan-Yan
Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University
Shinojima, Naoki
Department of Neurosurgery, Faculty of Life Sciences, Kumamoto University
Kuroda, Jun-Ichiro
Department of Neurosurgery, Faculty of Life Sciences, Kumamoto University
Mukasa, Akitake
Department of Neurosurgery, Faculty of Life Sciences, Kumamoto University
Tomizawa, Kazuhito
Neutron Therapy Research Center, Okayama University
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| Abstract | 2-Methylthio-N-6-isopentenyl modification of adenosine (ms(2)i(6)A) is an evolutionally conserved modification found in mitochondrial (mt)-tRNAs. Cdk5 regulatory subunit-associated protein 1 (CDK5RAP1) specifically converts N6-isopentenyladenosine (i(6)A) to ms(2)i(6)A at position A37 of four mt-DNA-encoded tRNAs, and the modification regulates efficient mitochondrial translation and energy metabolism in mammals. Here, we report that the ms 2 conversion mediated by CDK5RAP1 in mt-tRNAs is required to sustain glioma-initiating cell (GIC)-related traits. CDK5RAP1 maintained the self-renewal capacity, undifferentiated state, and tumorigenic potential of GICs. This regulation was not related to the translational control of mt-proteins. CDK5RAP1 abrogated the antitumor effect of i(6)A by converting i(6)A to ms (2)i(6) A and protected GICs from excessive autophagy triggered by i(6)A. The elevated activity of CDK5RAP1 contributed to the amelioration of the tumor-suppressive effect of i(6)A and promoted GIC maintenance. This work demonstrates that CDK5RAP1 is crucial for the detoxification of endogenous i(6)A and that GICs readily utilize this mechanism for survival.
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| Published Date | 2019-11-22
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| Publication Title |
iScience
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| Volume | volume21
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| Publisher | Cell Press
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| Start Page | 42
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| End Page | 56
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| ISSN | 2589-0042
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| Content Type |
Journal Article
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| language |
English
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| OAI-PMH Set |
岡山大学
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| Copyright Holders | © 2019 The Author(s).
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| File Version | publisher
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| PubMed ID | |
| DOI | |
| Web of Science KeyUT | |
| Related Url | isVersionOf https://doi.org/10.1016/j.isci.2019.10.012
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| License | http://creativecommons.org/licenses/by-nc-nd/4.0/
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