THE GENE ENCODING IFP 53 TRYPTOPHANYL-TRANSFER-RNA SYNTHETASE IS REGULATED BY THE GAMMA-INTERFERON ACTIVATION FACTOR/

We have obtained genomic DNA encoding the interferon-gamma (IFN-gamma) -inducible IFP 53/tryptophanyl-tRNA synthetase. Comparison with severa l different IFP 53 cDNA clones revealed a complex pattern of alternati vely spliced 5'-untranslated regions. The interferon-responsive region within the IFP 53 promoter was found to contain a gamma-interferon ac tivation site (GAS) but not the interferon-stimulated response element and to bind the gamma-interferon activation factor (GAF). GAF.GAS com plexes contained the IFN-regulated 91-kDa protein. Competition experim ents defined the GAS boundaries and showed that GAF binding to the IFP 53 GAS could be prevented by an excess of the IFN-gamma response regi ons of several other IFN-gamma-inducible genes. We thus provide eviden ce for a central role of GAS.GAF in gene transcription mediated by IFN -gamma and suggest a consensus sequence defining more precisely the re quirements for GAF binding to DNA.