| Project/Area Number |
16K07339
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Cell biology
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | RNA / USP15 / TUT1 / RNA代謝 / Sparcl1 / Sart3 / RNA splicing / spliceosome / cerebellum / motor dysfunctions / RNAスプライシング / スプライシング / 脳神経疾患 / ユビキチン |
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| Outline of Final Research Achievements |
In this study, we report that deubiquitinating enzyme, ubiquitin specific peptidase 15 (USP15), regulates neuronal functions by controlling the RNA metabolism. We found that lack of USP15 in mice induces impairment in motor ability with cerebellar malfunction. We also found that USP15 deubiquitinates terminal uridylyl transferase 1 (TUT1), which is responsible for polyuridylation of U6-snRNA, a core factor of spliceosome. TUT1 is normally localized on nucleolus via K63-linked ubiquitination; however, TUT1 redistributed from nucleolus to nucleoplasm after deubiquitination. Lack of USP15 reduced U6-snRNA levels and also widely affects splicing patterns of multiple genes, including Sparcl1. Thus, our results suggest that USP15 is important for spliceosomal functions through the regulation of TUT1, and lack of USP15 may trigger aberrant gene expression related to the maintenance of cerebellar functions and enhance the risk of developing neurodegenerative disorder.
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| Academic Significance and Societal Importance of the Research Achievements |
本課題では、脱ユビキチン化酵素USP15の機能解析を行い、USP15がRNA代謝制御に関わることを見出した。またUSP15の下流で制御される標的遺伝子も同定した。USP15は神経変性疾患をはじめとする様々な疾患との関連性も報告されており、本課題の成果は、これまで明らかにされていなかった疾患のメカニズム解明にもつながる可能性があると考えている。
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