2022 Fiscal Year Final Research Report
Depletion of ribosomal proteins and mRNA-specific translation control: studying the molecular pathogenesis of congenital anemia
Project/Area Number |
19K08869
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 54010:Hematology and medical oncology-related
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Research Institution | University of Miyazaki |
Principal Investigator |
Uechi Tamayo 宮崎大学, 医学部, 准教授 (10381104)
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Project Period (FY) |
2019-04-01 – 2023-03-31
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Keywords | リボソームタンパク質 / 先天性貧血 / ゼブラフィッシュ / 翻訳 |
Outline of Final Research Achievements |
The ribosome is a cellular component responsible for synthesizing proteins and found within all cells. However, abnormalities in the ribosome can lead to specific tissue abnormalities. We speculated that this is because of the presence of different translation regulatory mechanisms in each tissue. To investigate the molecular mechanism of congenital anemia, a representative disease, we developed zebrafish anemia model by suppressing the expression of a specific ribosomal protein gene and attempted to elucidate the mechanism that causes anemia. As a result, we found that not only genes involved in hematopoiesis but also a gene involved in the biosynthesis of glycans showed decreased translation efficiency. Additionally, we confirmed that overexpression of the gene leads to the recovery of red blood cell count. We concluded that the gene-specific translation regulatory mechanism involving ribosomal proteins is necessary for normal erythropoiesis.
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Free Research Field |
分子遺伝学
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Academic Significance and Societal Importance of the Research Achievements |
ヒトのリボソームは79種類のタンパク質と4種類のRNAで構成され、RNAは約200箇所で化学修飾を受ける複雑な構造体である。タンパク質や修飾の翻訳における役割は未解明であり、リボソームの組み立てを担う因子も含めて、いずれかの異常は様々な先天性疾患との関連が示唆され、将来的にがんを発症しやすいこともわかってきた。これらリボソーム病の発症メカニズムの解明は、治療法の開発や創薬に必須である。先天性貧血モデルを用いて新たな知見が得られたことは、リボソーム病の解明に向けた重要な基盤情報になると考える。
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