2022 Fiscal Year Final Research Report
Structural basis for the sequence-specific RNA-recognition mechanism of a human splicing regulatory protein
| Project/Area Number |
18K06093
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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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| Review Section |
Basic Section 43020:Structural biochemistry-related
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| Research Institution | Musashino University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
井上 裕介 群馬大学, 大学院理工学府, 教授 (90304302)
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Keywords | pre-mRNAスプライシング |
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| Outline of Final Research Achievements |
The splicing regulatory protein is thought to contribute to the suppression of tumorigenesis by regulating the alternative splicing of genes involved in apoptosis. However, the number and types of genes regulated by the protein, as well as its target sequences and recognition mechanisms, are unknown. In this study, we aimed to elucidate the splicing regulation mechanism mediated by the protein using structural and functional analyses.
We prepared the RNA-binding region of the protein and attempted to co-crystallize it with RNA fragments containing the putative target sequence. We also tried to suppress the expression of this protein in cultured cells to analyze the effect of this protein on splicing.
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| Free Research Field |
構造生物学
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| Academic Significance and Societal Importance of the Research Achievements |
がん細胞においてスプライシング因子の遺伝子に高頻度に変異が生じていることが報告され，mRNA前駆体スプライシングを作用点とする抗がん剤の開発が期待されてきている。しかし，これらの多くの研究の場合，「スプライシングに必須の基本的な因子で，かつ，複数の因子」が対象になっており，実際に特異性をもつ阻害剤を開発するのは困難である。しかし，本研究で対象としているスプライシング制御蛋白質は，この一つの蛋白質が選択的スプライシングを制御することで限定された複数の遺伝子の発現に影響を与える点が特徴であり，抗がん剤への開発に繋がる可能が高く，研究する価値は十分に高いと考えている。
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