Abstract
We have investigated the transcriptional control elements of the human interferon (IFN)-gamma-induced tryptophanyl-tRNA synthetase (hWRS) gene and characterized the transcripts. Transcription leads to a series of mRNAs with different combinations of the first exons. The full-length 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. This alternatively spliced mRNA is probably translated into a 48-kDa protein starting from Met48 in exon III. The predicted 48-kDa protein corresponds exactly to an IFN-gamma-inducible protein previously detected by two-dimensional gel electrophoresis. By isolation of genomic clones and construction of plasmids containing hWRS promoter fragments fused to the secreted alkaline phosphatase reporter gene we have mapped a promoter region essential for IFN-mediated gene activation. This region contains IFN-stimulated response elements (ISRE) as well as a Y-box and a gamma-activated sequence (GAS) element. IFN-gamma inducibility of hWRS depends on ongoing protein synthesis, suggesting that so far undescribed transcription factors apart from the latent GAS-binding protein p91 contribute to gene activation. This could be interferon-regulatory factor-1, which binds ISRE elements.
Highlights
We have investigated the transcriptional control elements of the human interferon (IFN)-y-induced tryptophanyl-tRNA synthetase gene and characterized the transcripts
IFN-y inducibility of hWRS depends on ongoing protein synthesis, suggesting that so far undescribed transcription factors apart from the latent GASbinding protein p9I contribute to gene activation
Apart from the antiviral effect that led to the discovery oflFNs, these are recognized as factors eliciting multiple effects in target cells, such as antitumor activity, antigrowth activity, immunoregulatory activity, as well as effects on the differentiation of various cells [1,2,3]
Summary
Vol 270, No., Issue of January 6, pp. 397-403, 1995 Printed in U.S.A. Transcriptional Regulation of the Interferon-y-inducible Tryptophanyl-tRNA Synthetase Includes Alternative Splicing*. IFN-y inducibility of hWRS depends on ongoing protein synthesis, suggesting that so far undescribed transcription factors apart from the latent GASbinding protein p9I contribute to gene activation. This could be interferon-regulatory factor-I, which binds ISRE elements. As tryptophan is a common substrate for IDO and hWRS, a link between the IFN-,,-induced functional effects of these proteins appears likely, because the two genes are regulated in a very similar way by IFN-" The induction of both enzymes by IFN-" is dependent on protein synthesis in most cell lines.
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