@article{8a331ca8c85a4a8099a574958656f14c,
title = "FTO Demethylates Cyclin D1 mRNA and Controls Cell-Cycle Progression",
abstract = "N6-Methyladenosine (m6A) modification is the major chemical modification in mRNA that controls fundamental biological processes, including cell proliferation. Herein, we demonstrate that fat mass and obesity-associated (FTO) demethylates m6A modification of cyclin D1, the key regulator for G1 phase progression and controls cell proliferation in vitro and in vivo. FTO depletion upregulates cyclin D1 m6A modification, which in turn accelerates the degradation of cyclin D1 mRNA, leading to the impairment of G1 progression. m6A modification of cyclin D1 oscillates in a cell-cycle-dependent manner; m6A levels are suppressed during the G1 phase and enhanced during other phases. Low m6A levels during G1 are associated with the nuclear translocation of FTO from the cytosol. Furthermore, nucleocytoplasmic shuttling of FTO is regulated by casein kinase II-mediated phosphorylation of FTO. Our results highlight the role of m6A in regulating cyclin D1 mRNA stability and add another layer of complexity to cell-cycle regulation.",
keywords = "casein kinase, cell cycle, cyclin D1, FTO, modification, N-methyladenosine, phosphorylation, RNA",
author = "Mayumi Hirayama and Wei, {Fan Yan} and Takeshi Chujo and Shinya Oki and Maya Yakita and Daiki Kobayashi and Norie Araki and Nozomu Takahashi and Ryoji Yoshida and Hideki Nakayama and Kazuhito Tomizawa",
note = "Funding Information: We thank Dr. Shinjiro Hino (Kumamoto University) for advice regarding the data analysis and Ms. Nobuko Maeda and Dr. Toshiro Moroishi for technical assistance. We thank Dr. Shuichi Kawashiri and Dr. Koroku Kato (Department of Oral and Maxillofacial Surgery, Kanazawa University Graduate School of Medical Science, Ishikawa 920-8641, Japan) for providing the HOC313 cells. This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Sciences, and Technology of Japan ( 17905074 and 18959602 to K.T.; 18H02599 and 18K19521 to F.-Y.W.), the Japan Agency for Medical Research and Development (AMED; 17935694 to K.T.), the Takeda Science Foundation (to K.T.), and the Japan Science and Technology Agency (JST; to F.-Y.W. and S.O.). Publisher Copyright: {\textcopyright} 2020 The Author(s)",
year = "2020",
month = apr,
day = "7",
doi = "10.1016/j.celrep.2020.03.028",
language = "English",
volume = "31",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "1",
}
