Poster abstracts
Poster number 35 submitted by Colton Martens
Role of EPRS and BEX1 in the post-transcriptional control of pro-inflammatory genes in the heart
Colton R. Martens (Department of Physiology and Cell Biology, College of Medicine, The Ohio State University; Molecular, Cellular, and Developmental Biology, The Ohio State University), Lisa E. Dorn, Federica Accornero
Abstract:
Given the well-established role of chronic inflammation in the onset of many diseases, it is essential that regulators of inflammatory genes are characterized. Aside from its role in charging tRNAs, Glutamyl-prolyl-tRNA synthetase (EPRS) has non-canonical functions in regulating select inflammatory mRNAs. Upon stimulation by inflammatory signals, EPRS associates with the GAIT complex and inhibits the translation of inflammatory genes. A 12-16 hour lag time between the inflammatory signal and the GAIT-mediated attenuation of the inflammatory response suggests that this is a mechanism to prevent maladaptive prolonged inflammation. Our lab has identified BEX1 as a novel binding partner of EPRS in the heart. BEX1 is increased in failing hearts, where it stabilizes pro-inflammatory mRNAs. Consistent with excessive inflammation as a cause of heart failure, mice overexpressing BEX1 are more susceptible to chronic stress-induced heart failure while mice lacking BEX1 are protected. We are currently investigating the significance of the EPRS/BEX1 interaction in the regulation of inflammation. Additionally, we are studying the role of BEX1 in regulating pathogen-induced inflammatory responses. Specifically, we are looking at BEX1-mediated immune response in hearts infected with a cardiotropic virus. Preliminary results suggest that BEX1 serves a cardioprotective role in the context of infection. The maladaptive effect of BEX1 in response to chronic stress and the apparent adaptive role of BEX1 in response to a transient immune stress fit the paradigm in which acute inflammatory responses are essential for maintenance of homeostasis while chronic inflammation is maladaptive.
Keywords: Inflammation, EPRS, BEX1