This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Berlioz, C. Articles by Darlix, J. L. Search for Related Content PubMed PubMed Citation Articles by Berlioz, C. Articles by Darlix, J. L.

 Previous Article  |  Next Article 

J. Virol., Apr 1995, 2214-2222, Vol 69, No. 4
Copyright © 1995, American Society for Microbiology

An internal ribosomal entry mechanism promotes translation of murine leukemia virus gag polyprotein precursors

C Berlioz and JL Darlix
LaboRetro, Unite de Virologie Humaine (INSERM-ENS U412), Ecole Normale Superieure de Lyon, France.

The genomic retroviral RNA is the messenger for the translation of the gag and pol genes encoding the precursors to the major structural proteins and enzymes, respectively, of the virion core. The long 5' untranslated region, the leader, is formed of independent well- structured domains involved in key steps of the viral life cycle such as the initiation of proviral DNA synthesis, genomic RNA dimerization and packaging, and the initiation of gag translation. These functional features and the presence of stable secondary structures between the cap and the gag initiation codon suggested that translation initiation of gag might proceed through a mechanism different from the canonical ribosome scanning process. Interestingly enough, murine leukemia viruses code also for a glycosylated gag precursor, named glyco-gag, initiated at a CUG codon upstream and in the same open reading frame as the AUGgag. We have investigated the translation initiation of gag and glyco-gag precursors of Friend murine leukemia virus (F-MLV) in the rabbit reticulocyte lysate system and in murine cells. Through site- directed mutagenesis of gag and glyco-gag initiation codons, we show that initiation of gag and glyco-gag synthesis does not utilize the classical ribosome scanning. When poliovirus protease 2A is coexpressed in murine cells, expression of MLV-lacZ RNA is not modified, indicating that translation initiation of MLV gag precursors is a cap-independent mechanism. In addition, the F-MLV leader was inserted between two genes in a dicistronic neo-MLV-lacZ mRNA, and its ability to promote expression was examined in vitro and in vivo. Results obtained demonstrate that an internal ribosome entry mechanism promotes translation of F-MLV gag precursors. This finding led us to construct a new dicistronic retroviral vector in which the F-MLV leader can promote both packaging of recombinant genomic RNA and expression of the 3' gene.

This article has been cited by other articles:

• Yoshimura, F. K., Luo, X., Zhao, X., Gerard, H. C., Hudson, A. P. (2008). Up-regulation of a cellular protein at the translational level by a retrovirus. Proc. Natl. Acad. Sci. USA 105: 5543-5548 [Abstract] [Full Text]  
• Camerini, V., Decimo, D., Balvay, L., Pistello, M., Bendinelli, M., Darlix, J.-L., Ohlmann, T. (2008). A Dormant Internal Ribosome Entry Site Controls Translation of Feline Immunodeficiency Virus. J. Virol. 82: 3574-3583 [Abstract] [Full Text]  
• Anderson, J. L., Johnson, A. T., Howard, J. L., Purcell, D. F. J. (2007). Both Linear and Discontinuous Ribosome Scanning Are Used for Translation Initiation from Bicistronic Human Immunodeficiency Virus Type 1 env mRNAs. J. Virol. 81: 4664-4676 [Abstract] [Full Text]  
• Bolinger, C., Yilmaz, A., Hartman, T. R., Kovacic, M. B., Fernandez, S., Ye, J., Forget, M., Green, P. L., Boris-Lawrie, K. (2007). RNA helicase A interacts with divergent lymphotropic retroviruses and promotes translation of human T-cell leukemia virus type 1. Nucleic Acids Res 0: gkm124v1-14 [Abstract] [Full Text]  
• Gabus, C., Ivanyi-Nagy, R., Depollier, J., Bucheton, A., Pelisson, A., Darlix, J.-L. (2006). Characterization of a nucleocapsid-like region and of two distinct primer tRNALys,2 binding sites in the endogenous retrovirus Gypsy. Nucleic Acids Res 34: 5764-5777 [Abstract] [Full Text]  
• Baird, S. D., Turcotte, M., Korneluk, R. G., Holcik, M. (2006). Searching for IRES. RNA 12: 1755-1785 [Abstract] [Full Text]  
• Jern, P., Sperber, G. O., Ahlsen, G., Blomberg, J. (2005). Sequence Variability, Gene Structure, and Expression of Full-Length Human Endogenous Retrovirus H. J. Virol. 79: 6325-6337 [Abstract] [Full Text]  
• RONFORT, C., DE BREYNE, S., SANDRIN, V., DARLIX, J.-L., OHLMANN, T. (2004). Characterization of two distinct RNA domains that regulate translation of the Drosophila gypsy retroelement. RNA 10: 504-515 [Abstract] [Full Text]  
• Alvarez, E., Menendez-Arias, L., Carrasco, L. (2003). The Eukaryotic Translation Initiation Factor 4GI Is Cleaved by Different Retroviral Proteases. J. Virol. 77: 12392-12400 [Abstract] [Full Text]  
• Meignin, C., Bailly, J.-L., Arnaud, F., Dastugue, B., Vaury, C. (2003). The 5' Untranslated Region and Gag product of Idefix, a Long Terminal Repeat-Retrotransposon from Drosophila melanogaster, Act Together To Initiate a Switch between Translated and Untranslated States of the Genomic mRNA. Mol. Cell. Biol. 23: 8246-8254 [Abstract] [Full Text]  
• Jaag, H. M., Kawchuk, L., Rohde, W., Fischer, R., Emans, N., Prufer, D. (2003). An unusual internal ribosomal entry site of inverted symmetry directs expression of a potato leafroll polerovirus replication-associated protein. Proc. Natl. Acad. Sci. USA 100: 8939-8944 [Abstract] [Full Text]  
• Brasey, A., Lopez-Lastra, M., Ohlmann, T., Beerens, N., Berkhout, B., Darlix, J.-L., Sonenberg, N. (2003). The Leader of Human Immunodeficiency Virus Type 1 Genomic RNA Harbors an Internal Ribosome Entry Segment That Is Active during the G2/M Phase of the Cell Cycle. J. Virol. 77: 3939-3949 [Abstract] [Full Text]  
• Beasley, B. E., Hu, W.-S. (2002). cis-Acting Elements Important for Retroviral RNA Packaging Specificity. J. Virol. 76: 4950-4960 [Abstract] [Full Text]  
• Butsch, M., Boris-Lawrie, K. (2002). Destiny of Unspliced Retroviral RNA: Ribosome and/or Virion?. J. Virol. 76: 3089-3094 [Full Text]  
• Hellen, C. U.T., Sarnow, P. (2001). Internal ribosome entry sites in eukaryotic mRNA molecules. Genes Dev. 15: 1593-1612 [Full Text]  
• Martínez-Salas, E., Ramos, R., Lafuente, E., López de Quinto, S. (2001). Functional interactions in internal translation initiation directed by viral and cellular IRES elements. J. Gen. Virol. 82: 973-984 [Full Text]  
• Low, W., Harries, M., Ye, H., Du, M.-Q., Boshoff, C., Collins, M. (2001). Internal Ribosome Entry Site Regulates Translation of Kaposi's Sarcoma-Associated Herpesvirus FLICE Inhibitory Protein. J. Virol. 75: 2938-2945 [Abstract] [Full Text]  
• Ohlen, C., Kalos, M., Hong, D. J., Shur, A. C., Greenberg, P. D. (2001). Expression of a Tolerizing Tumor Antigen in Peripheral Tissue Does Not Preclude Recovery of High-Affinity CD8+ T Cells or CTL Immunotherapy of Tumors Expressing the Antigen. J. Immunol. 166: 2863-2870 [Abstract] [Full Text]  
• Buck, C. B., Shen, X., Egan, M. A., Pierson, T. C., Walker, C. M., Siliciano, R. F. (2001). The Human Immunodeficiency Virus Type 1 gag Gene Encodes an Internal Ribosome Entry Site. J. Virol. 75: 181-191 [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]  
• Hu, W.-S., Pathak, V. K. (2000). Design of Retroviral Vectors and Helper Cells for Gene Therapy. Pharmacol. Rev. 52: 493-512 [Abstract] [Full Text]  
• Roberts, T. M., Boris-Lawrie, K. (2000). The 5' RNA Terminus of Spleen Necrosis Virus Stimulates Translation of Nonviral mRNA. J. Virol. 74: 8111-8118 [Abstract] [Full Text]  
• van Hall, T., Sijts, A., Camps, M., Offringa, R., Melief, C., Kloetzel, P.-M., Ossendorp, F. (2000). Differential Influence on Cytotoxic T Lymphocyte Epitope Presentation by Controlled Expression of Either Proteasome Immunosubunits or PA28. J. Exp. Med. 192: 483-494 [Abstract] [Full Text]  
• Anderson, J. A., Pathak, V. K., Hu, W.-S. (2000). Effect of the Murine Leukemia Virus Extended Packaging Signal on the Rates and Locations of Retroviral Recombination. J. Virol. 74: 6953-6963 [Abstract] [Full Text]  
• Ohlmann, T., Lopez-Lastra, M., Darlix, J.-L. (2000). An Internal Ribosome Entry Segment Promotes Translation of the Simian Immunodeficiency Virus Genomic RNA. J. Biol. Chem. 275: 11899-11906 [Abstract] [Full Text]  
• 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]  
• 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]  
• Lopez-Lastra, M., Ulrici, S., Gabus, C., Darlix, J.-L. (1999). Identification of an Internal Ribosome Entry Segment in the 5' Region of the Mouse VL30 Retrotransposon and Its Use in the Development of Retroviral Vectors. J. Virol. 73: 8393-8402 [Abstract] [Full Text]  
• Isoyama, T., Kamoshita, N., Yasui, K., Iwai, A., Shiroki, K., Toyoda, H., Yamada, A., Takasaki, Y., Nomoto, A. (1999). Lower concentration of La protein required for internal ribosome entry on hepatitis C virus RNA than on poliovirus RNA. J. Gen. Virol. 80: 2319-2327 [Abstract] [Full Text]  
• Dinauer, M. C., Li, L. L., Bjorgvinsdottir, H., Ding, C., Pech, N. (1999). Long-Term Correction of Phagocyte NADPH Oxidase Activity by Retroviral-Mediated Gene Transfer in Murine X-Linked Chronic Granulomatous Disease. Blood 94: 914-922 [Abstract] [Full Text]  
• Hildinger, M., Abel, K. L., Ostertag, W., Baum, C. (1999). Design of 5' Untranslated Sequences in Retroviral Vectors Developed for Medical Use. J. Virol. 73: 4083-4089 [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]  
• Gan, W., Celle, M. L., Rhoads, R. E. (1998). Functional Characterization of the Internal Ribosome Entry Site of eIF4G mRNA. J. Biol. Chem. 273: 5006-5012 [Abstract] [Full Text]  
• Nanbru, C., Lafon, I., Audigier, S., Gensac, M.-C., Vagner, S., Huez, G., Prats, A.-C. (1997). Alternative Translation of the Proto-oncogene c-myc by an Internal Ribosome Entry Site. J. Biol. Chem. 272: 32061-32066 [Abstract] [Full Text]  
• Gan, W., Rhoads, R. E. (1996). Internal Initiation of Translation Directed by the 5`-Untranslated Region of the mRNA for eIF4G, a Factor Involved in the Picornavirus-induced Switch from Cap-dependent to Internal Initiation. J. Biol. Chem. 271: 623-626 [Abstract] [Full Text]  
• Malbec, O., Schmitt, C., Bruhns, P., Krystal, G., Fridman, W. H., Daeron, M. (2001). Src Homology 2 Domain-containing Inositol 5-Phosphatase 1 Mediates Cell Cycle Arrest by Fcgamma RIIB. J. Biol. Chem. 276: 30381-30391 [Abstract] [Full Text]