METTL6 is a tRNA m3C methyltransferase that regulates pluripotency and tumor cell growth
Menée in vitro et à l'aide d'une xénogreffe sur un modèle murin, cette étude démontre que la protéine METTL6 est une méthyltransférase qui catalyse la formation de la 3-méthylcytidine en position 32 de l'ARN de transfert spécifique de la sérine et régule la pluripotence ainsi que la croissance des cellules tumorales
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.
Science Advances 2020