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Effects of intercistronic length on the efficiency of reinitiation by eucaryotic ribosomes.

Department of Biological Sciences, University of Pittsburgh, Pennsylvania 15260.

ABSTRACT

Simian virus 40-based plasmids that direct the synthesis of preproinsulin during short-term transfection of COS cells have been used to probe the mechanism of reinitiation by eucaryotic ribosomes. Earlier studies from several laboratories had established that the ability of ribosomes to reinitiate translation at an internal AUG codon depends on having a terminator codon in frame with the preceding AUG triplet and upstream from the intended restart site. In the present studies, the position of the upstream terminator codon relative to the preproinsulin restart site has been systematically varied. The efficiency of reinitiation progressively improved as the intercistronic sequence was lengthened. When the upstream "minicistron" terminated 79 nucleotides before the preproinsulin start site, the synthesis of proinsulin was as efficient as if there were no upstream AUG codons. A mechanism is postulated that might account for this result, which is somewhat surprising inasmuch as bacterial ribosomes reinitiate less efficiently as the intercistronic gap is widened.

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• Arita, M., Shimizu, H., Miyamura, T. (2004). Characterization of in vitro and in vivo phenotypes of poliovirus type 1 mutants with reduced viral protein synthesis activity. J. Gen. Virol. 85: 1933-1944 [Abstract] [Full Text]  
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• Gutierrez, S., Kikhno, I., Lopez Ferber, M. (2004). Transcription and promoter analysis of pif, an essential but low-expressed baculovirus gene. J. Gen. Virol. 85: 331-341 [Abstract] [Full Text]  
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• Kos, M., Denger, S., Reid, G., Gannon, F. (2002). Upstream Open Reading Frames Regulate the Translation of the Multiple mRNA Variants of the Estrogen Receptor alpha. J. Biol. Chem. 277: 37131-37138 [Abstract] [Full Text]  
• Heppner Goss, K., Trzepacz, C., Tuohy, T. M. F., Groden, J. (2002). Attenuated APC alleles produce functional protein from internal translation initiation. Proc. Natl. Acad. Sci. USA 99: 8161-8166 [Abstract] [Full Text]  
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• Kozak, M. (2001). Constraints on reinitiation of translation in mammals. Nucleic Acids Res 29: 5226-5232 [Abstract] [Full Text]  
• Jousse, C., Bruhat, A., Carraro, V., Urano, F., Ferrara, M., Ron, D., Fafournoux, P. (2001). Inhibition of CHOP translation by a peptide encoded by an open reading frame localized in the chop 5'UTR. Nucleic Acids Res 29: 4341-4351 [Abstract] [Full Text]  
• DAS, M., HARVEY, I., CHU, L. L., SINHA, M., PELLETIER, J. (2001). Full-length cDNAs: more than just reaching the ends. Physiol. Genomics 6: 57-80 [Abstract] [Full Text]  
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• Chang, P.-J., Liu, S.-T. (2001). Function of the Intercistronic Region of BRLF1-BZLF1 Bicistronic mRNA in Translating the Zta Protein of Epstein-Barr Virus. J. Virol. 75: 1142-1151 [Abstract] [Full Text]  
• Deffaud, C., Darlix, J.-L. (2000). Rous Sarcoma Virus Translation Revisited: Characterization of an Internal Ribosome Entry Segment in the 5' Leader of the Genomic RNA. J. Virol. 74: 11581-11588 [Abstract] [Full Text]  
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• Liu, H., Jang, J. K., Graham, J., Nycz, K., McKim, K. S. (2000). Two Genes Required for Meiotic Recombination in Drosophila Are Expressed From a Dicistronic Message. Genetics 154: 1735-1746 [Abstract] [Full Text]  
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• Deffaud, C., Darlix, J.-L. (2000). Characterization of an Internal Ribosomal Entry Segment in the 5' Leader of Murine Leukemia Virus env RNA. J. Virol. 74: 846-850 [Abstract] [Full Text]  
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• Niepel, M., Gallie, D. R. (1999). Identification and Characterization of the Functional Elements within the Tobacco Etch Virus 5' Leader Required for Cap-Independent Translation. J. Virol. 73: 9080-9088 [Abstract] [Full Text]  
• LaPierre, L. A., Holzschu, D. L., Bowser, P. R., Casey, J. W. (1999). Sequence and Transcriptional Analyses of the Fish Retroviruses Walleye Epidermal Hyperplasia Virus Types 1 and 2: Evidence for a Gene Duplication. J. Virol. 73: 9393-9403 [Abstract] [Full Text]  
• Child, S. J., Miller, M. K., Geballe, A. P. (1999). Translational Control by an Upstream Open Reading Frame in the HER-2/neu Transcript. J. Biol. Chem. 274: 24335-24341 [Abstract] [Full Text]  
• Remm, M., Remm, A., Ustav, M. (1999). Human Papillomavirus Type 18 E1 Protein Is Translated from Polycistronic mRNA by a Discontinuous Scanning Mechanism. J. Virol. 73: 3062-3070 [Abstract] [Full Text]  
• Pilipenko, E. V., Viktorova, E. G., Khitrina, E. V., Maslova, S. V., Jarousse, N., Brahic, M., Agol, V. I. (1999). Distinct Attenuation Phenotypes Caused by Mutations in the Translational Starting Window of Theiler's Murine Encephalomyelitis Virus. J. Virol. 73: 3190-3196 [Abstract] [Full Text]  
• Arnaud, E., Touriol, C., Boutonnet, C., Gensac, M.-C., Vagner, S., Prats, H., Prats, A.-C. (1999). A New 34-Kilodalton Isoform of Human Fibroblast Growth Factor 2 Is Cap Dependently Synthesized by Using a Non-AUG Start Codon and Behaves as a Survival Factor. Mol. Cell. Biol. 19: 505-514 [Abstract] [Full Text]  
• Wang, L., Wessler, S. R. (1998). Inefficient Reinitiation Is Responsible for Upstream Open Reading Frame –Mediated Translational Repression of the Maize R Gene. Plant Cell 10: 1733-1746 [Abstract] [Full Text]  
• Lincoln, A. J., Monczak, Y., Williams, S. C., Johnson, P. F. (1998). Inhibition of CCAAT/Enhancer-binding Protein alpha  and beta  Translation by Upstream Open Reading Frames. J. Biol. Chem. 273: 9552-9560 [Abstract] [Full Text]  
• Pestova, T. V., Shatsky, I. N., Fletcher, S. P., Jackson, R. J., Hellen, C. U.T. (1998). A prokaryotic-like mode of cytoplasmic eukaryotic ribosome binding to the initiation codon during internal translation initation of hepatitis C and classical swine fever virus RNAs. Genes Dev. 12: 67-83 [Abstract] [Full Text]  
• Bullock, T. N.J., Patterson, A. E., Franlin, L. L., Notidis, E., Eisenlohr, L. C. (1997). Initiation Codon Scanthrough versus Termination Codon Readthrough Demonstrates Strong Potential for Major Histocompatibility Complex Class I-restricted Cryptic Epitope Expression. J. Exp. Med. 186: 1051-1058 [Abstract] [Full Text]  
• Gunnery, S., Maivali, U., Mathews, M. B. (1997). Translation of an Uncapped mRNA Involves Scanning. J. Biol. Chem. 272: 21642-21646 [Abstract] [Full Text]  
• Mori, Y., Matsubara, H., Murasawa, S., Kijima, K., Maruyama, K., Tsukaguchi, H., Okubo, N., Hamakubo, T., Inagami, T., Iwasaka, T., Inada, M. (1996). Translational Regulation of Angiotensin II Type 1A Receptor: Role of Upstream AUG Triplets. Hypertension 28: 810-817 [Abstract] [Full Text]  
• Walker, W. H., Girardet, C., Habener, J. F. (1996). Alternative Exon Splicing Controls a Translational Switch from Activator to Repressor Isoforms of Transcription Factor CREB during Spermatogenesis. J. Biol. Chem. 271: 20219-21050 [Abstract] [Full Text]  
• Yueh, A, Schneider, R J (1996). Selective translation initiation by ribosome jumping in adenovirus-infected and heat-shocked cells.. Genes Dev. 10: 1557-1567 [Abstract]  
• Wera, S., Fernandez, A., Lamb, N. J. C., Turowski, P., Hemmings-Mieszczak, M., Mayer-Jaekel, R. E., Hemmings, B. A. (1995). Deregulation of Translational Control of the 65-kDa Regulatory Subunit (PR65alpha) of Protein Phosphatase 2A Leads to Multinucleated Cells. J. Biol. Chem. 270: 21374-21381 [Abstract] [Full Text]  
• Oliveira, C. C., McCarthy, J. E. G. (1995). The Relationship between Eukaryotic Translation and mRNA Stability. J. Biol. Chem. 270: 8936-8943 [Abstract] [Full Text]  
• Chen, P. C.-H., DuBois, G. C., Chen, M.-J. (1995). Mapping the Domain(s) Critical for the Binding of Human Tumor Necrosis Factor-alpha to Its Two Receptors. J. Biol. Chem. 270: 2874-2878 [Abstract] [Full Text]  
• Pulak, R, Anderson, P (1993). mRNA surveillance by the Caenorhabditis elegans smg genes.. Genes Dev. 7: 1885-1897 [Abstract]  
• von Melchner, H, DeGregori, J V, Rayburn, H, Reddy, S, Friedel, C, Ruley, H E (1992). Selective disruption of genes expressed in totipotent embryonal stem cells.. Genes Dev. 6: 919-927 [Abstract]  
• Miller, P F, Hinnebusch, A G (1989). Sequences that surround the stop codons of upstream open reading frames in GCN4 mRNA determine their distinct functions in translational control.. Genes Dev. 3: 1217-1225 [Abstract]  
• Kalderon, D, Rubin, G M (1988). Isolation and characterization of Drosophila cAMP-dependent protein kinase genes.. Genes Dev. 2: 1539-1556 [Abstract]  
• Pooggin, M. M., Hohn, T., Futterer, J. (2000). Role of a Short Open Reading Frame in Ribosome Shunt on the Cauliflower Mosaic Virus RNA Leader. J. Biol. Chem. 275: 17288-17296 [Abstract] [Full Text]  
• Ryabova, L. A., Pooggin, M. M., Dominguez, D. I., Hohn, T. (2000). Continuous and Discontinuous Ribosome Scanning on the Cauliflower Mosaic Virus 35 S RNA Leader Is Controlled by Short Open Reading Frames. J. Biol. Chem. 275: 37278-37284 [Abstract] [Full Text]  
• Gizard, F., Lavallee, B., DeWitte, F., Hum, D. W. (2001). A Novel Zinc Finger Protein TReP-132 Interacts with CBP/p300 to Regulate Human CYP11A1 Gene Expression. J. Biol. Chem. 276: 33881-33892 [Abstract] [Full Text]