Poster abstracts
Poster number 8 submitted by Anindhya Sundar Das
Aminoacyl-tRNA synthetase complex-interacting multifunctional protein 3 (AIMP3) is essential for cardiac homeostasis
Anindhya Sundar Das (Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus 43210, USA), Charles P. Rabolli (Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus 43210, USA), Colton R. Martens (Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus 43210, USA), Federica Accornero (Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus 43210, USA)
Abstract:
In eukaryotes, tRNA multi-synthetase complex (MSC) has been proposed to evolve to facilitate protein synthesis by efficiently providing charged tRNAs to the translating ribosome. The human MSC consists of 8 aminoacyl-tRNA synthetases (aaRS) and 3 non-enzymatic proteins known as aminoacyl-tRNA synthetase complex-interacting multifunctional proteins (AIMP1, 2, and 3). Aside from their role in translation, these multifunctional proteins are involved in other biological processes such as inflammation, apoptosis, and DNA damage response. However, their functions in specialized cells such as cardiomyocytes (CM) have not been studied. Here, we report that CM-specific conditional knockout (cKO) of AIMP3 in mice induces severe fibrosis and leads to immune cell infiltration concomitant with pathological cardiac remodeling. AIMP3 cKO mice show significant impairment of cardiac function, which ultimately develops heart failure within one month of deletion. The global protein synthesis is unperturbed in CMs from cKO hearts, suggesting that AIMP3 plays a critical translation-independent role in maintaining physiological cardiac functions and homeostasis. Currently, we are probing into the key cellular defects and their molecular mechanisms in cKO hearts that might help us to understand the CM-specific functions of AIMP3 with a therapeutic potential for the treatment of heart failure.
Keywords: tRNA multi-synthetase complex, AIMP3, Cardiac function