Using a combination of in vitro and in vivo screens, scientists from the Helmholtz-Zentrum München and colleagues identified the RNA-modifying enzyme METTL6 as a potential new oncogene. In line with findings that loss of METTL6 inhibits liver cancer cell proliferation and impaired colony formation capacity, low expression of METTL6 correlates with increased survival of patients with hepatocellular carcinoma. Mettl6 KO mice did not display overt morphological defects, but they showed impaired metabolism, such as reduced metabolic and impaired glucose response. RNA methyltransferases such as METTL6 could thus represent novel therapeutic targets for antiproliferative cancer drugs and may help to understand the links between cancer and metabolic dysfunction.
METTL6 is a tRNA m3C methyltransferase that regulates pluripotency and tumor cell growth.
Ignatova VV, Kaiser S, Ho JSY, Bing X, Stolz P, Tan YX, Lee CL, Gay FPH, Lastres PR, Gerlini R, Rathkolb B, Aguilar-Pimentel 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, de Angelis MH, Bultmann S, Rando OJ, Guccione E, Kellner SM, Schneider R. Sci Adv. 2020 Aug 26;6(35):eaaz4551. doi: 10.1126/sciadv.aaz4551. eCollection 2020 Aug.
*This article has been written by our colleagues at the German Mouse Clinic (GMC). Its full version is available here.