FTO Demethylates Cyclin D1 mRNA and Controls Cell-Cycle Progression

Mayumi Hirayama, Fan Yan Wei, Takeshi Chujo, Shinya Oki, Maya Yakita, Daiki Kobayashi, Norie Araki, Nozomu Takahashi, Ryoji Yoshida, Hideki Nakayama, Kazuhito Tomizawa

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number107464
JournalCell Reports
Volume31
Issue number1
DOIs
Publication statusPublished - Apr 7 2020

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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    Hirayama, M., Wei, F. Y., Chujo, T., Oki, S., Yakita, M., Kobayashi, D., Araki, N., Takahashi, N., Yoshida, R., Nakayama, H., & Tomizawa, K. (2020). FTO Demethylates Cyclin D1 mRNA and Controls Cell-Cycle Progression. Cell Reports, 31(1), [107464]. https://doi.org/10.1016/j.celrep.2020.03.028