Alternative splicing regulation of the titin gene in dilated cardiomyopathy.

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670398
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: KUROYANAGI Hidehito 東京医科歯科大学, 難治疾患研究所, 准教授 (30323702)
• Project Period (FY): 2014-04-01 – 2016-03-31
• 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

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.

Free Research Field

分子生物学