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Molecular and Cellular Biology, April 2000, p. 2755-2759, Vol. 20, No. 8
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Translation of NRF mRNA Is Mediated by Highly Efficient Internal Ribosome Entry

A. Oumard, M. Hennecke, H. Hauser, and M. Nourbakhsh*

Department of Gene Regulation and Differentiation, National Research Institute for Biotechnology, D-38124 Braunschweig, Germany

Received 18 October 1999/Returned for modification 12 November 1999/Accepted 30 December 1999

The ubiquitous transcription factor NRF (NF-kappa B repressing factor) is a constitutive transcriptional silencer of the multifunctional cytokine interferon-beta . NRF mRNA contains a long 5' untranslated region (5'UTR) predicted to fold into a strong secondary structure. The presence of stable hairpins is known to be incompatible with efficient translation by ribosomal scanning. Using dicistronic reporter gene constructs, we show that the NRF 5'UTR acts as an internal ribosome entry site (IRES) which directs ribosomes to the downstream start codon by a cap-independent mechanism. The relative activity of this IRES in various cell lines is at least 30-fold higher than that of picornaviral IRESs. The NRF 5'UTR also functions as a translational enhancer in the context of monocistronic mRNAs. Our results indicate that the NRF 5'UTR contains a highly potent IRES, which may allow for an alternate mode of translation under physiological conditions in which cap-dependent translation is inhibited.

* Corresponding author. Mailing address: GBF-National Research Institute for Biotechnology, Mascheroder Weg 1, D-38124 Braunschweig, Germany. Phone: 5316181250. Fax: 5316181262. E-mail: mno{at}gbf.de.

Molecular and Cellular Biology, April 2000, p. 2755-2759, Vol. 20, No. 8
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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