Alternative splicing regulation of the titin gene in dilated cardiomyopathy.
| Project/Area Number |
26670398
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Cardiovascular medicine
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | タイチン / 拡張型心筋症 / mRNA / 選択的スプライシング / RBM20 / リン酸化 / 核移行 / スプライシング / 心筋症 / 受動的張力 / 細菌人工染色体 / 蛍光レポーター |
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| Outline of Final Research Achievements |
We have constructed fluorescence splicing reporter minigenes to visualize heart-specific alternative splicing of the TTN gene. We utilized the reporter system to analyze the heart-specific splicing regulation by RBM20. Mutations in the RBM20 gene identified in the dilated cardiomyopathy patients are enriched in the RSRSP stretch and we found that the RSRSP stretch is phosphorylated in cells and is crucial for RBM20 to be localized in the nucleus. The fluorescence TTN splicing reporter cell lines, RBM20-expressing cell lines and the anti-phospho-RBM20 antibody generated in this study can further be utilized in analyzing the effects of mutations in the RBM20 and screening for chemicals that can modify the function and localization of RBM20.
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Report
(3 results)
Research Products
(6 results)
