Molecular pathogenesis of ribosomopathies and defective ribosome CODE

2016 Fiscal Year Final Research Report

• Project/Area Number: 25291003
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Molecular biology
• Research Institution: University of Miyazaki
• Principal Investigator: Kenmochi Naoya 宮崎大学, フロンティア科学実験総合センター, 教授 (00133124)
• Co-Investigator(Renkei-kenkyūsha): Suzuki Tsutomu 東京大学, 工学研究科, 教授 (20292782) ; Suzuki Yutaka 東京大学, 新領域創成科学研究科, 教授 (40323646)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: リボソーム / 疾患モデル / ゼブラフィッシュ / 造血異常 / 核小体 / 発がん / 飜訳 / ダイアモンド・ブラックファン貧血

Outline of Final Research Achievements

Ribosomopathies are the diseases caused by ribosomal abnormalities. We hypothesized that the selected mRNA translation by ribosomes should play an important role in the disease onset. To investigate the molecular pathogenesis of ribosomopathies, we developed a zebrafish model of Diamond-Blackfun anemia by knocking down a ribosomal protein gene RPS19 and found that the genes involved in erythropoiesis and glycan biosynthesis were translationally down-regulated. We also investigated the role of rRNA modifications in zebrafish and found that the modifications are essential for the early development of zebrafish and a loss of the modification leads to translational dysregulation of mRNAs. These results indicate that regulation of the selected mRNA translation is associated with the pathogenic mechanism of ribosomopathies.

Free Research Field

分子遺伝学