| 研究実績の概要 |
2′-O-methylation is a modification of ribosomal RNA (rRNA), playing essential roles in development, cancer, and neurodegenerative diseases. However, its biological roles and the molecular mechanisms by which it regulates gene expression are largely unclear. Here, we show that a methyltransferase of 2′-O-methylation, Fbl, is essential for the temporal patterning of neural stem cells (NSCs), a process critical to establish highly ordered cortical layers. Fbl selectively regulates the translation of mRNAs involving in epigenetic regulator of histone H3 trimethylation at Lys27 (H3K27me3). The inhibition of H3K27me3 causes delays of the temporal pattern progression and impedes neurogenesis, thus phenocopying Fbl-mutant brains. Collectively, we found that 2′-O-methylation of rRNA by Fbl selectively regulates the translation of epigenetic regulators. This mechanism widens the range of epigenetic landscape, which notably impacts diverse developmental processes and diseases, and thus adds another level of complexity to physiologic and pathologic gene regulation.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
1: 当初の計画以上に進展している
理由
In this year, I have already identified targets of Fbl and found that Fbl selectively regulate translation of these targets. Moreover, I also found the mechanism by which Fbl regulates these targets. Now, I am preparing the manuscript for publishment. Therefre, the project progresses smoothly.
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