Transcriptional Regulation of the Interferon-
-inducible Tryptophanyl-tRNA Synthetase Includes Alternative Splicing (*)
- ↵¶ To whom correspondence should be addressed: Dept. of Molecular Biology, University of Aarhus, C:F: Møllers Allé, Bldg. 130, 8000 Aarhus C, DK. Tel.: 45-8942-3188; Fax: 45-8619-6500.
Abstract
We have investigated the transcriptional control elements of the human interferon (IFN)-
-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
Met
in exon III. The predicted 48-kDa protein corresponds exactly to an IFN-
-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 
-activated sequence (GAS) element. IFN-
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.
Footnotes
-
↵* This research was funded by the Danish National Research Council and by the Danish Cancer Society. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
- Received August 30, 1994.
- Revision received October 17, 1994.
- © 1995 by The American Society for Biochemistry and Molecular Biology, Inc.
