TY - JOUR
T1 - METTL6 is a tRNA m3C methyltransferase that regulates pluripotency and tumor cell growth
AU - Ignatova, Valentina V.
AU - Kaiser, Steffen
AU - Ho, Jessica Sook Yuin
AU - Bing, Xinyang
AU - Stolz, Paul
AU - Tan, Ying Xim
AU - Lee, Chee Leng
AU - Gay, Florence Pik Hoon
AU - Lastres, Palma Rico
AU - Gerlini, Raffaele
AU - Rathkolb, Birgit
AU - Aguilar-Pimentel, Antonio
AU - Sanz-Moreno, Adrián
AU - Klein-Rodewald, Tanja
AU - Calzada-Wack, Julia
AU - Ibragimov, Emil
AU - Valenta, Magdalena
AU - Lukauskas, Saulius
AU - Pavesi, Andrea
AU - Marschall, Susan
AU - Leuchtenberger, Stefanie
AU - Fuchs, Helmut
AU - Gailus-Durner, Valerie
AU - De Angelis, Martin Hrabe
AU - Bultmann, Sebastian
AU - Rando, Oliver J.
AU - Guccione, Ernesto
AU - Kellner, Stefanie M.
AU - Schneider, Robert
N1 - Publisher Copyright:
© 2020 The Authors.
PY - 2020/8
Y1 - 2020/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85090872221&partnerID=8YFLogxK
U2 - 10.1126/sciadv.aaz4551
DO - 10.1126/sciadv.aaz4551
M3 - Article
C2 - 32923617
AN - SCOPUS:85090872221
SN - 2375-2548
VL - 6
JO - Science advances
JF - Science advances
IS - 35
M1 - eaaz4551
ER -