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Differential regulation of mammalian tRNA synthetase genes by amino acid availability (818.7)
Author(s) -
Shan Jixiu,
Tang Tiffany,
Han Jaeseok,
Kaufman Randal,
Kilberg Michael
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.818.7
Subject(s) - atf4 , integrated stress response , biology , gene , transcription factor , unfolded protein response , amino acid , gene expression , eif4ebp1 , aminoacyl trna synthetase , transfer rna , protein biosynthesis , microbiology and biotechnology , genetics , messenger rna , translation (biology) , rna
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 response to AA deprivation. About one‐half of the genes for the cytoplasmic synthetases were up‐regulated and most required ATF4, but only a few of the mitochondrial synthetases were modestly increased and those were largely independent of ATF4. Genomic analysis of the ATF4‐dependent genes revealed the contribution of a C/EBP‐ATF response element (CARE) sequence. Grant Funding Source : Supported by NIH: DK092062, DK094729 (MSK); HL057346, DK042394, DK088227, HL052173, DK093074 (RJK)