2019 Fiscal Year Research-status Report
Functional analysis of an RNA methyltransferase in regulation of neural stem cell fate
| Project/Area Number |
18K14722
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
呉 泉 国立研究開発法人理化学研究所, 生命機能科学研究センター, 基礎科学特別研究員 (60812766)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | RNA modificaiton / Brain development / Temporal patterning |
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| Outline of Annual Research Achievements |
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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| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
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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| Strategy for Future Research Activity |
As I mentioned before, in this year, I will submit the manuscript of this project. I will perform experiments for review.
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| Causes of Carryover |
The budget will be used for performing the experiment of review. Specifically, sequencing fee, new reagent and softwares.
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