Poster abstracts
Poster number 44 submitted by Danni Jin
Interaction between Human Glutamyl-Prolyl Aminoacyl-tRNA Synthetase Linker Domain and HIV-1 Matrix: Implications for HIV-1 Infectivity
Danni Jin (Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH, 43210), Nathan Titkemeier, Alice Duchon (Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH, 43210), Yiping Zhu, Stephen P. Goff (Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University, New York, NY, 10032), Corine St. Gelias, Li Wu (Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210), Karin Musier-Forsyth (Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH, 43210)
Abstract:
The HIV-1 genome encodes 15 viral proteins, all of which have been shown to interact with host factors. These interactions can have either a positive or negative effect on viral replication. The HIV-1 Gag polyprotein is composed of 4 major functional domains: matrix (MA), capsid, nucleocapsid, and p6. Surprisingly, the MA interactome has been reported to include the components of the human multi-aminoacyl-tRNA synthetase complex (MSC) (Jäger, S., et al. (2012) Nature 481, 365-370). In this work, we map the specific site of MA interaction with the MSC to the bifunctional glutamyl-prolyl-tRNA synthetase (EPRS) protein. Our data also suggest that EPRS expression has a negative impact on HIV-1 infectivity and the virus has evolved to downregulate this essential host cell protein. In addition to their well-known physiological function in translation, many aminoacyl-tRNA synthetases, including EPRS, are mobilized from the MSC to function in a wide variety of non-translational pathways. Coimmunoprecipitation reveals that MA interacts with the linker sequence between the two synthetase domains of EPRS. Preliminary studies suggest that this interaction is RNA dependent. We are investigating the RNAs that are responsible for bridging the interaction. Candidate RNAs that are being investigated in vitro include human tRNAPro and tRNAGlu, and a structured RNA known as the GAIT element that the linker domain of EPRS has previously been shown to bind to in its role in translational regulation of genes involved in the inflammatory response.
Keywords: EPRS, HIV-1, RNA Binding Protein