The role of Cdkal1-mediated tRNA modification in peripheral neuropathy
| Project/Area Number |
15H04850
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Kumamoto University |
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Principal Investigator |
Kazuhito Tomizawa 熊本大学, 大学院生命科学研究部(医), 教授 (40274287)
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| Co-Investigator(Renkei-kenkyūsha) |
ARAKI Eiichi 熊本大学, 大学院生命科学研究部, 教授 (10253733)
USUKU Koichiro 熊本大学, 医学部附属病院, 教授 (30281223)
KAKUMA Tatsuyuki 久留米大学, バイオ統計センター, 教授 (50341540)
WEI Fan-Yan 熊本大学, 大学院生命科学研究部, 准教授 (90555773)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2017: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2016: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
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| Keywords | 糖尿病 / 神経障害 / tRNA / 翻訳 / 末梢神経 / 小胞体ストレス / 神経栄養因子 / タンパク質翻訳 / 核酸 / 生理学 / RNA / 糖尿病性神経障害 / Cdkal1 / 遺伝子改変動物 / 神経変性 |
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| Outline of Final Research Achievements |
Genetic variations in CDKAL1 have been associated with the development of type 2 diabetes. CDKAL1 is a methylthiotransferase that catalyzes 2-methylthi modification of tRNALys(UUU). The ms2 modification is important for accurate decoding of Lys codon in Proinsulin. In addition to Proinsulin, Lys is also critical for the processing of various neurotropic factors. We hypothesized that the dysregulation of CDKAL1 might cause aberrant translation of neurotropic factors, and lead to the development of neuropathy. To test this hypothesis, we investigated the sensory functions of peripheral nerves in Cdkal1-knockout mice. Cdkal1-deficiency induced peripheral neuropathy independent of glucose intolerance. Cdkal1-deficient mice exhibited loss of CGRP- and IB4-positive neurons in DRG. Cdkal1-deficient mice exhibited loss of nerve fibers in footpad. BDNF were reduced in DRG of Cdkal1KO mice.These results suggest that dysfunction of Cdkal1 may critical for development of diabetic neuropathy.
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Report
(4 results)
Research Products
(12 results)
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[Journal Article] Reactive sulfur species regulate tRNA methylthiolation and contribute to insulin secretion.2017
Author(s)
Takahashi, N., Wei, F.-Y., Watanabe, S., Hirayama, M., Ohuchi, Y., Fujimura, A., Kaitsuka, T., Sawa, T., Nakayama, H., Akaike, T. and Tomizawa, K.
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Journal Title
Nucl. Acid Res.
Volume: 45
Pages: 435-445
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Evolving specificity of tRNA 3-methyl-cytidine-32 (m3C32) modification: a subset of tRNAsSer require isopentenylation of A37.2016
Author(s)
Arimbasseri, A.G., Iben, J.R., Wei, F.-Y., Rijal, K., Tomizawa, K., Hafner, M., and Maraia, R.J.
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Journal Title
RNA
Volume: 22
Pages: 1400-1410
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Lack of tRNA-i6A37 modification causes mitochondrial-like metabolic deficiency in S. pombe by limiting activity of cytosolic tRNATyr, not mito-tRNA.2016
Author(s)
Lamichhane, T., Arimbasseri, A., Rijal, K., Iben, J.R., Wei, F.-Y., Tomizawa, K. and Maraia, R.J.
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Journal Title
RNA
Volume: 22
Pages: 583-596
Related Report
Peer Reviewed / Int'l Joint Research
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