2020 Fiscal Year Final Research Report
Elucidation of the mechanism by which RNA helicases regulate the functional relationship between nucleoli and stress granules.
Project/Area Number |
19K16133
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 44010:Cell biology-related
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Research Institution | Osaka Dental University |
Principal Investigator |
Hirai Yuya 大阪歯科大学, 歯学部, 助教 (90710369)
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Project Period (FY) |
2019-04-01 – 2021-03-31
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Keywords | RNAヘリカーゼ / DDX17 / 核小体 / ストレス顆粒 / 天然変性領域 / 液-液相分離 / membraneless organelles |
Outline of Final Research Achievements |
To elucidate the regulation mechanisms of functional relationship between nucleoli and stress granules (SGs), I focused on an RNA helicase, DDX17, and examined its subcellular localization and dynamics. DDX17 has two isoforms, p72 and p82. I revealed that p82, which contains additional intrinsically disordered regions (IDRs) compared with p72, localized at the nucleoli. P82 showed slower dynamics than p72. Although both p72 and p82 localized to the SGs under the stress condition, p72 was predominantly incorporated into the SGs. Furthermore, the enzymatic mutants of both p72 and p82 accumulated into the SGs. The enzymatic mutant of p82 abolished nucleolar localization of p82. These results suggest that DDX17 links nucleoli to SGs in the IDRs and enzymatic activity-dependent manners.
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Free Research Field |
細胞生物学
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Academic Significance and Societal Importance of the Research Achievements |
液-液相分離による膜を持たないオルガネラの構造制御機構の詳細が次々と明らかになっている。核小体とストレス顆粒は共に膜を持たないオルガネラであり、それらの機能的関連が示唆されるが、その詳細は明らかではない。本研究により、RNAヘリカーゼであるDDX17が、天然変性領域や酵素活性によってその核小体とストレス顆粒への局在を制御していることが明らかになった。本研究成果は、核小体とストレス顆粒の機能的関連のさらなる解明につながるため大きな学術的意義を持つ。また核小体とストレス顆粒は様々な疾患とも関連しており、これら疾患の治療法の開発にもつながることが期待され、社会的意義も大きい。
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