Translational control of Ybx1 expression regulates cardiac function in response to pressure overload in vivo

• DOI: 10.1007/s00395-023-00996-1
• Publication Date: 2023-06-28T15:03:08Z
• Authors: Eshita Varma; Jana Burghaus; Thomas Schwarzl; Thileepan Sekaran; Parul Gupta; Agnieszka A. Górska; Christoph Hofmann; Claudia Stroh; Lonny Jürgensen; Verena Kamuf-Schenk; Xue Li; Rebekka Medert; Florian Leuschner; Vivien Kmietczyk; Marc Freichel; Hugo A. Katus; Matthias W. Hentze; Norbert Frey; Mirko Völkers
• Keywords: Translational regulation; Pressure overload

Abstract RNA–protein interactions are central to cardiac function, but how activity of individual RNA-binding protein is regulated through signaling cascades in cardiomyocytes during heart failure development largely unknown. The mechanistic target rapamycin kinase a hub that controls mRNA translation cardiomyocytes; however, direct link between mTOR and proteins the has not been established. Integrative transcriptome translatome analysis revealed dependent translational upregulation RNA binding Ybx1 early pathological remodeling independent levels. necessary for cardiomyocyte growth by regulating synthesis. To identify molecular mechanisms regulates cellular synthesis, we identified mRNAs bound Ybx1. We discovered eucaryotic elongation factor 2 (Eef2) Ybx1, its upregulated hypertrophy on expression. Eef2 itself sufficient drive increasing global translation. Finally, depletion vivo preserved function hypertrophy. Thus, activation mTORC1 links altered gene expression regulation which turn promotes increased Eef2.