METTL6 is a tRNA m(3)C methyltransferase that regulates pluripotency and tumor cell growth

Ignatova, Valentina V.; Kaiser, Steffen; Ho, Jessica Sook Yuin; Bing, Xinyang; Stolz, Paul; Tan, Ying Xim; Lee, Chee Leng; Gay, Florence Pik Hoon; Lastres, Palma Rico; Gerlini, Raffaele; Rathkolb, Birgit; Aguilar-Pimentel, Antonio; Sanz-Moreno, Adrian; Klein-Rodewald, Tanja; Calzada-Wack, Julia; Ibragimov, Emil; Valenta, Magdalena; Lukauskas, Saulius; Pavesi, Andrea; Marschall, Susan; Leuchtenberger, Stefanie; Fuchs, Helmut; Gailus-Durner, Valerie; De Angelis, Martin Hrabe; Bultmann, Sebastian; Rando, Oliver J.; Guccione, Ernesto; Kellner, Stefanie M. und Schneider, Robert (2020): METTL6 is a tRNA m(3)C methyltransferase that regulates pluripotency and tumor cell growth. In: Science Advances, Bd. 6, Nr. 35, eaaz4551

Abstract

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 MettI6 in mouse stem cells results in changes in ribosome occupancy and RNA levels, as well as impaired pluripotency. In mice, MettI6 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Chemie und Pharmazie > Department Chemie
• Themengebiete: 500 Naturwissenschaften und Mathematik > 540 Chemie
• ISSN: 2375-2548
• Sprache: Englisch