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Molecular and Cellular Biology, April 2000, p. 2755-2759, Vol. 20, No. 8
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-
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
B repressing factor)
is a constitutive transcriptional silencer of the multifunctional cytokine interferon-
. 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.
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