PMID- 10733578 OWN - NLM STAT- MEDLINE DCOM- 20000425 LR - 20240314 IS - 0270-7306 (Print) IS - 1098-5549 (Electronic) IS - 0270-7306 (Linking) VI - 20 IP - 8 DP - 2000 Apr TI - Translation of NRF mRNA is mediated by highly efficient internal ribosome entry. PG - 2755-9 AB - The ubiquitous transcription factor NRF (NF-kappaB 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. FAU - Oumard, A AU - Oumard A AD - Department of Gene Regulation and Differentiation, National Research Institute for Biotechnology, D-38124 Braunschweig, Germany. FAU - Hennecke, M AU - Hennecke M FAU - Hauser, H AU - Hauser H FAU - Nourbakhsh, M AU - Nourbakhsh M LA - eng PT - Journal Article PL - United States TA - Mol Cell Biol JT - Molecular and cellular biology JID - 8109087 RN - 0 (5' Untranslated Regions) RN - 0 (DNA-Binding Proteins) RN - 0 (NKRF protein, human) RN - 0 (RNA, Messenger) RN - 0 (Repressor Proteins) RN - 0 (Transcription Factors) SB - IM MH - 3T3 Cells MH - 5' Untranslated Regions MH - Animals MH - Base Sequence MH - CHO Cells MH - Cricetinae MH - *DNA-Binding Proteins MH - HeLa Cells MH - Humans MH - Mice MH - Molecular Sequence Data MH - Plasmids MH - *Protein Biosynthesis MH - RNA, Messenger/*genetics MH - Repressor Proteins/*genetics MH - Ribosomes/*genetics MH - Transcription Factors/*genetics MH - Transfection PMC - PMC85491 EDAT- 2000/03/25 09:00 MHDA- 2000/04/29 09:00 PMCR- 2000/04/01 CRDT- 2000/03/25 09:00 PHST- 2000/03/25 09:00 [pubmed] PHST- 2000/04/29 09:00 [medline] PHST- 2000/03/25 09:00 [entrez] PHST- 2000/04/01 00:00 [pmc-release] AID - 1754 [pii] AID - 10.1128/MCB.20.8.2755-2759.2000 [doi] PST - ppublish SO - Mol Cell Biol. 2000 Apr;20(8):2755-9. doi: 10.1128/MCB.20.8.2755-2759.2000.