Verification of novel molecular mechanism of cardiac hypertrophy via regulation of mRNA degradation

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16004
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Osaka University
• Principal Investigator: Masumura Yuki 大阪大学, 医学系研究科, 特任研究員 (60793437)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 心肥大 / RNA代謝 / 次世代シークエンサー

Outline of Final Research Achievements

For exploratory research aimed at regulatory mechanisms of cardiac hypertrophy through new perspective of RNA metabolism, we applied two genome-wide analyses to reveal targets of negative regulator of RNA metabolism, Btg2, in cardiomyocytes. We performed RNA sequence and RNA immunoprecipitation using Btg2 specific antibody coupled with high throughput sequencing (RIP-seq) to obtain genome-wide binding profiles of Btg2. From these analysis, 52 genes were listed for candidate Btg2 targeted genes in cardiomyocytes, which are related to metabolism of RNA and protein synthesis. To perform molecular functional analysis of these candidate genes, we establish analysis method to measure intracellular calcium dynamics using imaging cytometry. We are now working on verification of cardiac phenotype and gene expression under hypertrophic stimulation using zebrafish. These candidate genes through our exploratory research are expected to be new regulatory factor of cardiac hypertrophy.

Free Research Field

心不全

Academic Significance and Societal Importance of the Research Achievements

従来心筋肥大に関する分子メカニズム解明の焦点は、遺伝子発現やタンパク合成であった。しかし、肥大刺激に対するmRNAの安定性の変化（RNA代謝の変化）については未知の部分が多く、次世代シークエンサーを用いて、Btg2を介したmRNAの安定性の網羅的解析は、従来とは全く異なったアプローチで心筋肥大の分子メカニズムに迫るものと考えられる。またRNA代謝という観点での研究は、RNAの質的・量的制御のメカニズムを通し、心臓の恒常性を維持していくメカニズムの解明にも今後つながっていくことが期待できる。