Translation of NRF mRNA is mediated by highly efficient internal ribosome entry

The ubiquitous transcription factor NRF (NF-kappa B repressing factor) is a constitutive transcriptional silencer of the multifunctional cytokine inte rferon-beta. NRF mRNA contains a Long 5' untranslated region (5'UTR) predic ted to fold into a strong secondary structure. The presence of stable hairp ins is known to be incompatible with efficient translation by ribosomal sca nning. Using dicistronic reporter gene constructs, we show that the NRF 5'U TR acts as an internal ribosome entry site (IRES) which directs ribosomes t o the downstream start codon by a cap-independent mechanism. The relative a ctivity 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 alterna te mode of translation under physiological conditions in which cap-dependen t translation is inhibited.