Abstract
Usually only cells exposed to virus, double-stranded RNA or other inducers synthesize interferon (IFN)1,2. Interferon mRNA appears 1–2 h after induction, peaks at 1.5–20 h and decays with a half life of about 30 min3–6. So far, it has not been determined whether induction of interferon is due to transient stabilization of a rapidly turning-over mRNA or to activation of transcription. To clarify this issue we transformed mouse L cells with a hybrid gene in which the 5′-flanking region of the human IFN-α1 gene was followed by the rabbit β-globin transcription unit. Correctly initiated β-globin RNA appeared only after viral induction, with the kinetics described for interferon mRNA7. Cells transformed with the converse construction, or with the complete rabbit β-globin gene, constitutively produced correctly initiated transcripts; viral infection decreased the level of transcripts. We conclude that induction acts by activating transcription rather than by reducing turnover, and that the regulatory elements are contained in the 5′-flanking region of the interferon gene.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Stewart, W. II. The Interferon System (Springer, New York, 1979).
Berg, K. Acta path. microbiol. immun. scand. Sect. C, Suppl. 279 (1982).
Raj, N. & Pitha, P. Proc. natn. Acad. Sci. U.S.A. 78, 7426–7430 (1981).
Cavalieri, R., Havell, E., Vilcek, J. & Pestka, S. Proc. natn. Acad. Sci. U.S.A. 74, 4415–4419 (1977).
Sehgal, P., Dobberstein, B. & Tamm, I. Proc. natn. Acad. Sci. U.S.A. 74, 3409–3413 (1977).
Morser, J. et al. J. gen. Virol. 44, 231–234 (1979).
Mantei, N. & Weissmann, C. Nature 297, 128–132 (1982).
Dierks, P., van Ooyen, A., Mantei, N. & Weissmann, C. Proc. natn. Acad. Sci. U.S.A. 78, 1411–1415 (1981).
Dierks, P. et al. Cell 32, 695–706 (1983).
Berk, A. J. & Sharp, P. A. Cell 12, 721–732 (1977).
Weaver, R. & Weissmann, C. Nucleic Acids Res. 7, 1175–1193 (1979).
Mantei, N., Boll, W. & Weissmann, C. Nature 281, 40–46 (1979).
Grosveld, G., de Bower, E., Shewmaker, C. K. & Flavell, R. A. Nature 295, 120–126 (1982).
Shaw, G. D. et al. Nucleic Acids Res. 11, 555–573 (1983).
Wilson, D. E. J. Virol. 2, 1–6 (1968).
Thacore, H. & Youngner, J. S. J. Virol. 6, 42–48 (1970).
Vollock, V. & Housman, D. Cell 23, 509–514 (1981).
Robins, D., Peacock, I., Seeburg, P. & Axel, R. Cell 29, 623–631 (1982).
Majo, K., Warren, R. & Palmiter, R. Cell 29, 99–108 (1982).
Pelham, H. R. B. Cell 30, 517–528 (1982).
Lee, F., Mulligan, R., Berg, P. & Ringold, G. Nature 294, 228–232 (1981).
Reyes, G. et al. Nature 297, 597–601 (1982).
Pitha, P. et al. Proc. natn. Acad. Sci. U.S.A. 79, 4337–4341 (1982).
Grosschedl, R. & Birnstiel, M. L. Proc. natn. Acad. Sci. U.S.A. 77, 1432–1436 (1980).
Benoist, C. & Chambon, P. Nature 290, 304–310 (1981).
Ragg, H. & Weissmann, C. Nature 303, 439–442 (1983).
Nagata, S., Mantei, N. & Weissmann, C. Nature 287, 401–408 (1980).
Chalberg, M. & Englund, P. Meth. Enzym. 65, 39–43 (1980).
van Ooyen, A., van den Berg, J., Mantei, N. & Weissmann, C. Science 206, 337–344 (1979).
Grunstein, D. & Hogness, D. Proc. natn. Acad. Sci. U.S.A. 72, 3961–3965 (1975).
Maxam, A. & Gilbert, W. Proc. natn. Acad. Sci. U.S.A. 74, 560–564 (1977).
Wilkie, N. et al. Nucleic Acids Res. 7, 859–877 (1979).
Aviv, H. & Leder, P. Proc. natn. Acad. Sci. U.S.A. 69, 1408–1412 (1972).
Bernardi, G. Meth. Enzym. 21, 95–147 (1971).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Weidle, U., Weissmann, C. The 5′-flanking region of a human IFN-α gene mediates viral induction of transcription. Nature 303, 442–446 (1983). https://doi.org/10.1038/303442a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/303442a0
This article is cited by
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.