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Nobel Regulation Mechanism of Cell Cycle
Mayumi Hirayama (Kazuhito Tomizawa)

The cell cycle is tightly controlled by cell cycle-specific cyclins and their cyclin-dependent kinases. Progression of the G1 phase is mainly controlled by Cyclin D1. Cyclin D1 is localized in the nucleus and reaches its maximum level before the S phase. At the end of the G1 phase and after entry of the S phase, Cyclin D1 is exported to the cytoplasm and degraded by the ubiquitin-proteasome system. In this study, we showed another regulation of the protein level of Cyclin D1 for the progression of G1 phase to S phase. FTO localized in nucleus, demethylated m6A modification of Cyclin D1, resulting in the stabilization and highly expression of cyclin D1 at the G1 phase. After entry of the S phase, FTO translocated to the cytoplasm and methylated cyclin D1 mRNA, resulting in the degradation of the mRNA and inhibition of the translation of Cyclin D1. These results suggest that cell-cycle progression is in part controlled by the dynamic oscillation of m6A modification of mRNAs, regulated by FTO. These findings highlight the importance of epitranscriptomic regulation of gene expression during the cell cycle.

Hirayama, M., Wei, F.-Y., Chujo, T., Oki, S., Yakita, M., Kobayashi, D., Araki, N., Takahashi, N., Yoshida, R., Hideki Nakayama, H., and Tomizawa, K. FTO demethylates cyclin D1 mRNA and controls cell-cycle progression. Cell Reports 31(1), 107464, 2020.

FTO demethylates m6A-modified cyclin D1 mRNA and sustains its expression at S phase. When cell goes into S phase, cyclin D1 mRNA is methylated and its protein synthesis is inhibited in addition to the degradation of Cyclin D1.

Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Japan