Dysregulation of mRNA decay in MYBPC3 hypertrophic cardiomyopathy (A08)

• Subject Area: Cardiology, Angiology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 464424253

In hypertrophic Cardiomyopathy (HCM), the underlying mutations frequently affect MBPC3 and cause premature termination of MBPC3 protein synthesis. We observed that nonsense-mediated mRNA decay (NMD) activation plays an important role in the pathogenesis of HCM. Here we propose to (I) investigate the effect of NMD activation on gene regulation in healthy and diseased human induced pluripotent stem cells (iPSC-CMs), (II) evaluate the functional relevance of NMD activation in genetic HCM mouse models, and (III) explore a more general role of NMD in the pathogenesis of other hereditary cardiomyopathies.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1550: Molecular Circuits of Heart Disease
• Applicant Institution: Ruprecht-Karls-Universität Heidelberg
• Project Heads: Dr. Timon Seeger; Professor Dr. Georg Stoecklin