Selected mRNA translation and congenital pure red-cell aplasia: Studying the molecular pathogenesis of the anemia using zebrafish as a model system

2015 Fiscal Year Final Research Report

• Project/Area Number: 24591556
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: University of Miyazaki
• Principal Investigator: UECHI Tamayo 宮崎大学, フロンティア科学実験総合センター, 研究員 (10381104)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: リボソームタンパク質遺伝子 / 翻訳異常 / ゼブラフィッシュ / ダイアモンド・ブラックファン貧血

Outline of Final Research Achievements

More than ten ribosomal protein (RP) genes have been identified in 60% of the Diamond-Blackfan anemia (DBA) patients. We speculated that translation efficiency of specific mRNAs required for erythropoiesis was altered due to RP gene mutations. To evaluate the impact of RP deficiency on translation, we carried out microarray analysis of total mRNAs and RNA-seq analysis of polysomal mRNAs using zebrafish model of DBA. Comparing the data from both analyses enabled us to calculate the net translation efficiency. We found that the expression of 75 genes was repressed by more than 50%. Eight genes among the most repressed 50 genes were found to be involved in hematopoiesis. In-vitro synthesized mRNA of one of these genes partially rescued the anemia phenotype in the DBA model. These data should provide an important clue to the pathogenesis of DBA.

Free Research Field

分子遺伝学