Selected mRNA translation and congenital pure red-cell aplasia: Studying the molecular pathogenesis of the anemia using zebrafish as a model system
| Project/Area Number |
24591556
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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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| Research Field |
Pediatrics
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| Research Institution | University of Miyazaki |
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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)
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| Project Period (FY) |
2012-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| 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 / リボソームタンパク質 / 骨髄不全 / リボソーム病 / ダイヤモンド・ブラックファン貧血 |
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| 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.
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Report
(5 results)
Research Products
(20 results)
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[Journal Article] scaRNAs regulate splicing and vertebrate heart development.2015
Author(s)
Patil, P., Kibiryeva, N., Uechi, T., Marshall, J., Artman, M., O'Brien, J.E., Kenmochi, N. and Bittel, D.C.
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Journal Title
Biochimica et Biophysica Acta-Molecular Basis of Disease
Volume: 未定
Issue: 8
Pages: 1619-1629
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Loss of function mutations in RPL27 and RPS27 identified by whole-exome sequencing in Diamond-Blackfan anaemia.2015
Author(s)
Wang R, Yoshida K, Toki T, Sawada T, Uechi T, Okuno Y, Sato-Otsubo A, Kudo K, Kamimaki I, Kanezaki R, Shiraishi Y, Chiba K, Tanaka H, Terui K, Sato T, Iribe Y, Ohga S, Kuramitsu M, Hamaguchi I, Ohara A, Hara J, et al.
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Journal Title
British Journal of Haematology
Volume: 168
Issue: 6
Pages: 854-864
DOI
Related Report
Peer Reviewed / Open Access
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