Effect of RPS3 Serine 149 mutation on gene expression in hiPSC-derived cardiomyocytes during Ang II administration
Angiotensin II (Ang II) treatment contributes to hypertrophic growth and mitochondrial dysfunction in hiPSC-derived cardiomyocytes. Here, we report enhanced RPS3 phosphorylation at serine 149 in nuclear compartment and abnormal mitochondrial biogenesis during Ang II incubation. Furthermore, RPS3 S149 mutation attenuated Ang II induced cardiomyocyte hypertrophy and improved mitochondrial biogenesis and dysfunction. Mechanistically, RPS3 Ser149 mutation promoted mitochondrial RNA stabilization and blunt Ang II induced mitochodnrial RNA alternative splicing for degradation, by which RPS3 dephosphorylation restored mitochondrial complex assembly in cardiomyocytes. Overall design: To evaluate function of RPS3 Serine 149 mutation in Ang II induced cardiomyocyte hypertrophy, we generated hiPSC with or without RPS3 serine 149 mutation and induced hiPSC to differentiate into cardiomyosytes following Ang II treatment.