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Ignatova, V.V. ; Kaiser, S.* ; Ho, J.S.Y.* ; Bing, X.* ; Stolz, P.* ; Tan, Y.X.* ; Lee, C.L.* ; Gay, F.P.H.* ; Lastres, P.R. ; Gerlini, R. ; Rathkolb, B. ; Aguilar-Pimentel, J.A. ; Sanz-Moreno, A. ; Klein-Rodewald, T. ; Calzada-Wack, J. ; Ibragimov, E. ; Valenta, M. ; Lukauskas, S. ; Pavesi, A.* ; Marschall, S. ; Leuchtenberger, S. ; Fuchs, H. ; Gailus-Durner, V. ; Hrabě de Angelis, M. ; Bultmann, S.* ; Rando, O.J.* ; Guccione, E.* ; Kellner, S.M.* ; Schneider, R.

METTL6 is a tRNA m3C methyltransferase that regulates pluripotency and tumor cell growth.

Sci. Adv. 6:eaaz4551 (2020)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Recently, covalent modifications of RNA, such as methylation, have emerged as key regulators of all aspects of RNA biology and have been implicated in numerous diseases, for instance, cancer. Here, we undertook a combination of in vitro and in vivo screens to test 78 potential methyltransferases for their roles in hepatocellular carcinoma (HCC) cell proliferation. We identified methyltransferase-like protein 6 (METTL6) as a crucial regulator of tumor cell growth. We show that METTL6 is a bona fide transfer RNA (tRNA) methyltransferase, catalyzing the formation of 3-methylcytidine at C32 of specific serine tRNA isoacceptors. Deletion of Mettl6 in mouse stem cells results in changes in ribosome occupancy and RNA levels, as well as impaired pluripotency. In mice, Mettl6 knockout results in reduced energy expenditure. We reveal a previously unknown pathway in the maintenance of translation efficiency with a role in maintaining stem cell self-renewal, as well as impacting tumor cell growth profoundly.
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Publication type Article: Journal article
Document type Scientific Article
Language english
Publication Year 2020
HGF-reported in Year 2020
ISSN (print) / ISBN 2375-2548
e-ISSN 2375-2548
Journal Science Advances
Quellenangaben Volume: 6, Issue: 35, Pages: , Article Number: eaaz4551 Supplement: ,
Publisher American Association for the Advancement of Science (AAAS)
Publishing Place Washington, DC [u.a.]
Reviewing status Peer reviewed
Institute(s) Institute of Functional Epigenetics (IFE)
Institute of Experimental Genetics (IEG)
POF-Topic(s) 30203 - Molecular Targets and Therapies
30201 - Metabolic Health
Research field(s) Helmholtz Diabetes Center
Genetics and Epidemiology
PSP Element(s) G-502800-001
G-500692-001
G-500600-001
DOI 10.1126/sciadv.aaz4551
Scopus ID 85090872221
PubMed ID 32923617
Erfassungsdatum 2020-10-27
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