Differential regulation of mammalian tRNA synthetase genes by amino acid availability (818.7)

A low protein diet or one deficient in an essential amino acid (AA) triggers wide-ranging changes in feeding behavior and gene expression. Mammalian cells have evolved capabilities to cope with this nutritional stress. Activation of either GCN2 (AA limitation) or PERK (ER stress) eIF2 kinases leads to a suppression of global protein synthesis but a paradoxical increase in the translation of selected mRNA species, among them is activating transcription factor 4 (ATF4). Elevated expression of ATF4 protein increases the transcription from a large number of genes involved in a wide spectrum of cellular functions. During ER stress, gene expression profiling showed that ATF4 interacts with another bZIP transcription factor, CHOP, to induce genes associated with protein synthesis, among them were selected tRNA synthetases. In this study, we have quantified the differential expression of all of the genes for the cytoplasmic and mitochondrial localized tRNA synthetases in both wild type and ATF4 KO MEFs in respons...