TRANSCRIPTIONAL REGULATION OF THE INTERFERON-GAMMA-INDUCIBLE TRYPTOPHANYL-TRANSFER-RNA SYNTHETASE INCLUDES ALTERNATIVE SPLICING

We have investigated the transcriptional control elements of the human interferon (IFN)-gamma-induced tryptophanyl-tRNA synthetase (hWRS) ge ne and characterized the transcripts. Transcription leads to a series of mRNAs with different combinations of the first exons. The full-leng th mRNA codes for a 55-kDa protein (hWRS), but a mRNA lacking exon II is present in almost as high amounts as the full-length transcript. Th is alternatively spliced mRNA is probably translated into a 48-kDa pro tein starting from Met(48) in exon III. The predicted 48-kDa protein c orresponds exactly to an IFN-gamma-inducible protein previously detect ed by two-dimensional gel electrophoresis. By isolation of genomic clo nes and construction of plasmids containing hWRS promoter fragments fu sed to the secreted alkaline phosphatase reporter gene we have mapped a promoter region essential for IFN-mediated gene activation. This reg ion contains IFN stimulated response elements (ISRE) as well as a Y-bo x and a gamma-activated sequence (GAS) element. IFN-gamma inducibility of hWRS depends on ongoing protein synthesis, suggesting that so far undescribed scribed transcription factors apart from the latent GAS-bi nding protein p91 contribute to gene activation. This could be interfe ron-regulatory factor-1, which binds ISRE elements.