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Programmed —1 Ribosomal Frameshift in the Human Immunodeficiency Virus of Type 1

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Recoding: Expansion of Decoding Rules Enriches Gene Expression

Part of the book series: Nucleic Acids and Molecular Biology ((NUCLEIC,volume 24))

Abstract

A programmed —1 ribosomal frameshift enables the human immunode-ficiency virus of type 1 (HIV-1) to produce its enzymes in a precise proportion relative to its structural proteins, which is necessary to control viral assembly and maturation. Here, we critically review models that account for this phenomenon, focusing on the most recent model, which postulates that the frameshift is triggered by an incomplete translocation and involves the slippage of three tRNAs. The effect of changes in the rate of translation initiation and elongation and the possible involvement of cellular factors in frameshifting are briefly examined. Finally, we highlight recent efforts intended to interfere with this type of frameshift as a strategy to develop novel anti-HIV drugs.

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References

  • Agris PF (2008) Bringing order to translation: the contributions of transfer RNA anticodon-domain modifications. EMBO Rep 9:629–635

    Article  PubMed  CAS  Google Scholar 

  • Baranov PV, Gesteland RF, Atkins JF (2004) P-site tRNA is a crucial initiator of ribosomal frameshifting. RNA 10:221–230

    Article  PubMed  CAS  Google Scholar 

  • Baril M, Dulude D, Gendron K, Lemay G, Brakier-Gingras L (2003a) Efficiency of a programmed —1 ribosomal frameshift in the different subtypes of the human immunodeficiency virus type 1 group M. RNA 9:1246—1253

    Google Scholar 

  • Baril M, Dulude D, Steinberg SV, Brakier-Gingras L (2003b) The frameshift stimulatory signal of human immunodeficiency virus type 1 group O is a pseudoknot. J Mol Biol 331:571–583

    Google Scholar 

  • Biswas P, Jiang X, Pacchia AL, Dougherty JP, Peltz SW (2004) The human immunodeficiency virus type 1 ribosomal frameshifting site is an invariant sequence determinant and an important target for antiviral therapy. J Virol 78:2082–2087

    Article  PubMed  CAS  Google Scholar 

  • Brass AL, Dykxhoorn DM, Benita Y, Yan N, Engelman A, Xavier RJ, Lieberman J, Elledge SJ (2008) Identification of host proteins required for HIV infection through a functional genomic screen. Science 319:921–926

    Article  PubMed  CAS  Google Scholar 

  • Brierley I, Dos Ramos FJ (2006) Programmed ribosomal frameshifting in HIV-1 and the SARS-CoV. Virus Res 119:29–42

    Article  PubMed  CAS  Google Scholar 

  • Brierley I, Meredith MR, Bloys AJ, Hagervall TG (1997) Expression of a coronavirus ribosomal frameshift signal in Escherichia coli: influence of tRNA anticodon modification on frameshifting. J Mol Biol 270:360–373

    Article  PubMed  CAS  Google Scholar 

  • Brierley I, Pennell S (2001) Structure and function of the stimulatory RNAs involved in programmed eukaryotic—1 ribosomal frameshifting. Cold Spring Harb Symp Quant Biol 66:233–248

    Article  PubMed  CAS  Google Scholar 

  • Brierley I, Pennell S, Gilbert RJ (2007) Viral RNA pseudoknots: versatile motifs in gene expression and replication. Nature Rev Microbiol 5:598–610

    Article  CAS  Google Scholar 

  • Brierley I, Rolley NJ, Jenner AJ, Inglis SC (1991) Mutational analysis of the RNA pseudoknot component of a coronavirus ribosomal frameshifting signal. J Mol Biol 220:889–902

    Article  PubMed  CAS  Google Scholar 

  • Brunelle MN, Brakier-Gingras L, Lemay G (2003) Replacement of murine leukemia virus readthrough mechanism by human immunodeficiency virus frameshift allows synthesis of viral proteins and virus replication. J Virol 77:3345–3350

    Article  PubMed  CAS  Google Scholar 

  • Carlson BA, Kwon SY, Chamorro M, Oroszlan S, Hatfield DL, Lee BJ (1999) Transfer RNA modification status influences retroviral ribosomal frameshifting. Virology 255:2–8

    Article  PubMed  CAS  Google Scholar 

  • Carlson BA, Mushinski JF, Henderson DW, Kwon SY, Crain PF, Lee BJ, Hatfield DL (2001) 1-Methylguanosine in place of Y base at position 37 in phenylalanine tRNA is responsible for its shiftiness in retroviral ribosomal frameshifting. Virology 279:130–135

    Article  PubMed  CAS  Google Scholar 

  • Daviter T, Gromadski KB, Rodnina MV (2006) The ribosome’s response to codon-anticodon mismatches. Biochimie 88:1001–1011

    Article  PubMed  CAS  Google Scholar 

  • Dinman JD, Richter S., Plant EP, Taylor RC, Hammell AB, Rana TM (2002) The frameshift signal of HIV-1 involves a potential intramolecular triplex RNA structure. Proc Natl Acad Sci USA 99:5331–5336

    Article  PubMed  CAS  Google Scholar 

  • Dinman JD, Ruiz-Echevarria MJ, Czaplinski K., Peltz SW (1997) Peptidyl-transferase inhibitors have antiviral properties by altering programmed —1 ribosomal frameshifting efficiencies: development of model systems. Proc Natl Acad Sci USA 94:6606–6611

    Article  PubMed  CAS  Google Scholar 

  • Dulude D, Baril M, Brakier-Gingras L (2002) Characterization of the frameshift stimulatory signal controlling a programmed –1 ribosomal frameshift in the human immunodeficiency virus type 1. Nucleic Acids Res 30:5094–5102

    Article  PubMed  CAS  Google Scholar 

  • Dulude D, Berchiche YA, Gendron K, Brakier-Gingras L, Heveker N (2006) Decreasing the frameshift efficiency translates into an equivalent reduction of the replication of the human immunodeficiency virus type 1. Virology 345:127–136

    Article  PubMed  CAS  Google Scholar 

  • Dulude D, Theberge-Julien G, Brakier-Gingras L, Heveker N (2008) Selection of peptides interfering with a ribosomal frameshift in the human immunodeficiency virus type 1. RNA 14:981–991

    Article  PubMed  CAS  Google Scholar 

  • Farabaugh PJ (1997) Programmed alternative reading of the genetic code: RG Landes Company. Austin, Texas, USA and Springer-Verlag, Heidelberg, Germany, pp 69–101

    Book  Google Scholar 

  • Frank J, Gao H, Sengupta J, Gao N, Taylor DJ (2007) The process of mRNA-tRNA translocation. Proc Natl Acad Sci USA 104:19671–19678

    Article  PubMed  CAS  Google Scholar 

  • Gao F, Bailes E, Robertson DL, Chen Y, Rodenburg CM, Michael SF, Cummins LB, Arthur LO, Peeters M., Shaw GM, Sharp PM, Hahn BH (1999) Origin of HIV-1 in the chimpanzee Pan troglodytes troglodytes. Nature 397:436–441

    Article  PubMed  CAS  Google Scholar 

  • Gaudin C, Mazauric MH, Traikia M, Guittet E, Yoshizawa S, Fourmy D (2005) Structure of the RNA signal essential for translational frameshifting in HIV-1. J Mol Biol 349:1024–1035

    Article  PubMed  CAS  Google Scholar 

  • Gendron K, Charbonneau J, Dulude D, Heveker N, Ferbeyre G, Brakier-Gingras L (2008) The presence of the TAR RNA structure alters the programmed —1 ribosomal frameshift efficiency of the human immunodeficiency virus type 1 (HIV-1) by modifying the rate of translation initiation. Nucleic Acids Res 36:30–40

    Article  PubMed  CAS  Google Scholar 

  • Gendron K, Dulude D, Lemay G, Ferbeyre G, Brakier-Gingras L (2005) The virion-associated Gag-Pol is decreased in chimeric Moloney murine leukemia viruses in which the readthrough region is replaced by the frameshift region of the human immunodeficiency virus type 1. Virology 334:342–352

    Article  PubMed  CAS  Google Scholar 

  • Grentzmann G, Ingram JA, Kelly PJ, Gesteland RF, Atkins JF (1998) A dual-luciferase reporter system for studying recoding signals. RNA 4:479–486

    Article  PubMed  CAS  Google Scholar 

  • Harger JW, Dinman JD (2003) An in vivo dual-luciferase assay system for studying translational recoding in the yeast Saccharomyces cerevisiae. RNA 9:1019–1024

    Article  PubMed  CAS  Google Scholar 

  • Howard MT, Gesteland RF, Atkins JF (2004) Efficient stimulation of site-specific ribosome frameshifting by antisense oligonucleotides. RNA 10:1653–1661

    Article  PubMed  CAS  Google Scholar 

  • Hung M, Patel P, Davis S, Green SR (1998) Importance of ribosomal frameshifting for human immunodeficiency virus type 1 particle assembly and replication. J Virol 72:4819–4824

    PubMed  CAS  Google Scholar 

  • Jacks T, Madhani HD, Masiarz FR, Varmus HE (1988a) Signals for ribosomal frameshifting in the Rous sarcoma virus gag-pol region. Cell 55:447–458

    Google Scholar 

  • Jacks T., Power MD, Masiarz FR, Luciw PA, Barr PJ, Varmus HE (1988b) Characterization of ribosomal frameshifting in HIV-1 gag-pol expression. Nature 331:280–283

    Google Scholar 

  • Jenner L, Rees B, Yusupov M, Yusupova G (2007) Messenger RNA conformations in the ribosomal E site revealed by X-ray crystallography. EMBO Rep 8:846–850

    Article  PubMed  CAS  Google Scholar 

  • Karacostas V, Wolffe EJ, Nagashima K, Gonda MA, Moss B (1993) Overexpression of the HIV-1 gag-pol polyprotein results in intracellular activation of HIV-1 protease and inhibition of assembly and budding of virus-like particles. Virology 193:661–671

    Article  PubMed  CAS  Google Scholar 

  • Kollmus H, Hentze MW, Hauser H (1996) Regulated ribosomal frameshifting by an RNA-protein interaction. RNA 2:316–323

    PubMed  CAS  Google Scholar 

  • Kontos H, Napthine S, Brierley I (2001) Ribosomal pausing at a frameshifter RNA pseudoknot is sensitive to reading phase but shows little correlation with frameshift efficiency. Mol Cell Biol 21:8657–8670

    Article  PubMed  CAS  Google Scholar 

  • Léger M, Dulude D, Steinberg SV, Brakier-Gingras L (2007) The three transfer RNAs occupying the A, P and E sites on the ribosome are involved in viral programmed —1 ribosomal frameshift. Nucleic Acids Res 35:5581–5592

    Article  PubMed  Google Scholar 

  • Léger M, Sidani S, Brakier-Gingras L (2004) A reassessment of the response of the bacterial ribosome to the frameshift stimulatory signal of the human immunodeficiency virus type 1. RNA 10:1225–1235

    Article  PubMed  Google Scholar 

  • Liiv A, O’Connor M (2006) Mutations in the intersubunit bridge regions of 23S rRNA. J Biol Chem 281:29850–29862

    Article  PubMed  CAS  Google Scholar 

  • Lopinski JD, Dinman JD, Bruenn JA (2000) Kinetics of ribosomal pausing during programmed —1 translational frameshifting. Mol Cell Biol 20:1095–1103

    Article  PubMed  CAS  Google Scholar 

  • Marcheschi RJ, Staple DW, Butcher SE (2007) Programmed ribosomal frameshifting in SIV is induced by a highly structured RNA stem-loop. J Mol Biol 373:652–663

    Article  PubMed  CAS  Google Scholar 

  • McNaughton BR, Gareiss PC, Miller BL (2007) Identification of a selective small-molecule ligand for HIV-1 frameshift-inducing stem-loop RNA from an 11,325 member resin bound dynamic combinatorial library. J Am Chem Soc 129:11306–11307

    Article  PubMed  CAS  Google Scholar 

  • Michiels PJ, Versleijen AA, Verlaan PW, Pleij CW, Hilbers CW, Heus HA (2001) Solution structure of the pseudoknot of SRV-1 RNA, involved in ribosomal frameshifting. J Mol Biol 310:1109–1123

    Article  PubMed  CAS  Google Scholar 

  • Moran SJ, Flanagan JF, Namy O, Stuart DI, Brierley I, Gilbert RJ (2008) The mechanics of translocation: a molecular “spring-and-ratchet” system. Structure 16:664–672

    Article  PubMed  CAS  Google Scholar 

  • Namy O, Moran SJ, Stuart DI, Gilbert RJ, Brierley I (2006) A mechanical explanation of RNA pseudoknot function in programmed ribosomal frameshifting. Nature 441:244–247

    Article  PubMed  CAS  Google Scholar 

  • Nierhaus KH (2006) Decoding errors and the involvement of the E-site. Biochimie 88:1013–1019

    Article  PubMed  CAS  Google Scholar 

  • Nilsson J, Sengupta J, Frank J, Nissen P (2004) Regulation of eukaryotic translation by the RACK1 protein: a platform for signalling molecules on the ribosome. EMBO Rep 5:1137–1141

    Article  PubMed  CAS  Google Scholar 

  • Olsthoorn RC, Laurs M, Sohet F, Hilbers CW, Heus HA, Pleij CW (2004) Novel application of sRNA: stimulation of ribosomal frameshifting. RNA 10:1702–1703

    Article  PubMed  CAS  Google Scholar 

  • Parisien M, Major F (2008) The MC-Fold and MC-Sym pipeline infers RNA structure from sequence data. Nature 452:51–55

    Article  PubMed  CAS  Google Scholar 

  • Park J, Morrow CD (1991) Overexpression of the gag-pol precursor from human immunodeficiency virus type 1 proviral genomes results in efficient proteolytic processing in the absence of virion production. J Virol 65:5111–5117

    PubMed  CAS  Google Scholar 

  • Parkin NT, Chamorro M, Varmus HE (1992) Human immunodeficiency virus type 1 gag-pol frameshifting is dependent on downstream mRNA secondary structure: demonstration by expression in vivo. J Virol 66:5147–5151

    PubMed  CAS  Google Scholar 

  • Paul CP, Barry JK, Dinesh-Kumar SP, Brault V, Miller WA (2001) A sequence required for —1 ribosomal frameshifting located four kilobases downstream of the frameshift site. J Mol Biol 310:987–999

    Article  PubMed  CAS  Google Scholar 

  • Plant EP, Dinman JD (2006) Comparative study of the effects of heptameric slippery site composition on —1 frameshifting among different eukaryotic systems. RNA 12:666–673

    Article  PubMed  CAS  Google Scholar 

  • Plant EP, Jacobs KL, Harger JW, Meskauskas A, Jacobs JL, Baxter JL, Petrov AN, Dinman JD (2003) The 9-A solution: how mRNA pseudoknots promote efficient programmed —1 ribosomal frameshifting. RNA 9:168–174

    Article  PubMed  CAS  Google Scholar 

  • Rodnina MV, Gromadski KB, Kothe U, Wieden HJ (2005) Recognition and selection of tRNA in translation. FEBS Lett 579:938–942

    Article  PubMed  CAS  Google Scholar 

  • Sanders CL, Curran JF (2007) Genetic analysis of the E site during RF2 programmed frameshifting. RNA 13:1483–1491

    Article  PubMed  CAS  Google Scholar 

  • Sengupta J, Nilsson J, Gursky R, Spahn CM, Nissen P, Frank J (2004) Identification of the versatile scaffold protein RACK1 on the eukaryotic ribosome by cryo-EM. Nature Struct Mol Biol 11:957–962

    Article  CAS  Google Scholar 

  • Sharp PM, Bailes E, Chaudhuri RR, Rodenburg CM, Santiago MO, Hahn BH (2001) The origins of acquired immune deficiency syndrome viruses: where and when? Phil Trans Roy Soc (Lond.) 356:867–876

    Article  CAS  Google Scholar 

  • Shehu-Xhilaga M, Crowe SM, Mak J (2001) Maintenance of the Gag/Gag-Pol ratio is important for human immunodeficiency virus type 1 RNA dimerization and viral infectivity. J Virol 75:1834–1841

    Article  PubMed  CAS  Google Scholar 

  • Shen LX, Cai Z, Tinoco I Jr (1995) RNA structure at high resolution. FASEB J 9:1023–1033

    PubMed  CAS  Google Scholar 

  • Simon F, Mauclere P, Roques P, Loussert-Ajaka I, Muller-Trutwin MC, Saragosti S, Georges-Courbot MC, Barre-Sinoussi F, Brun-Vezinet F (1998) Identification of a new human immunodeficiency virus type 1 distinct from group M and group O. Nat Med 4:1032–1037

    Article  PubMed  CAS  Google Scholar 

  • Somogyi P, Jenner AJ, Brierley I, Inglis SC (1993) Ribosomal pausing during translation of an RNA pseudoknot. Mol Cell Biol 13:6931–6940

    PubMed  CAS  Google Scholar 

  • Staple DW, Butcher SE (2005) Solution structure and thermodynamic investigation of the HIV-1 frameshift inducing element. J Mol Biol 349:1011–1023

    Article  PubMed  CAS  Google Scholar 

  • Staple DW, Venditti V, Niccolai N, Elson-Schwab L, Tor Y, Butcher SE (2008) Guanidinoneomycin B recognition of an HIV-1 RNA helix. Chembiochem 9:93–102

    Article  PubMed  CAS  Google Scholar 

  • Su L, Chen L, Egli M, Berger JM, Rich A (1999) Minor groove RNA triplex in the crystal structure of a ribosomal frameshifting viral pseudoknot. Nature Struct Biol 6:285–292

    Article  PubMed  CAS  Google Scholar 

  • Takyar S, Hickerson RP, Noller HF (2005) mRNA helicase activity of the ribosome. Cell 120:49–58

    Article  PubMed  CAS  Google Scholar 

  • Telenti A, Martinez R, Munoz M, Bleiber G, Greub G, Sanglard D, Peters S (2002) Analysis of natural variants of the human immunodeficiency virus type 1 gag-pol frameshift stem-loop structure. J Virol 76:7868–7873

    Article  PubMed  CAS  Google Scholar 

  • Tu C, Tzeng TH, Bruenn JA (1992) Ribosomal movement impeded at a pseudoknot required for frameshifting. Proc Natl Acad Sci USA 89:8636–8640

    Article  PubMed  CAS  Google Scholar 

  • Vickers TA, Ecker DJ (1992) Enhancement of ribosomal frameshifting by oligonucleotides targeted to the HIV gag-pol region. Nucleic Acids Res 20:3945–3953

    Article  PubMed  CAS  Google Scholar 

  • Waas WF, Druzina Z, Hanan M, Schimmel P (2007) Role of a tRNA base modification and its precursors in frameshifting in eukaryotes. J Biol Chem 282:26026–26034

    Article  PubMed  CAS  Google Scholar 

  • Weiss RB, Dunn DM, Shuh M, Atkins JF, Gesteland RF (1989) E. coli ribosomes re-phase on retroviral frameshift signals at rates ranging from 2 to 50 percent. New Biol 1:159–169.

    PubMed  CAS  Google Scholar 

  • Wen JD, Lancaster L, Hodges C, Zeri AC, Yoshimura SH, Noller HF, Bustamante C, Tinoco I (2008) Following translation by single ribosomes one codon at a time. Nature 452:598–603

    Article  PubMed  CAS  Google Scholar 

  • Yelverton E, Lindsley D, Yamauchi P, Gallant JA (1994) The function of a ribosomal frameshifting signal from human immunodeficiency virus-1 in Escherichia coli. Mol Microbiol 11:303–313

    Article  PubMed  CAS  Google Scholar 

  • Yu ET, Zhang Q, Fabris D (2005) Untying the FIV frameshifting pseudoknot structure by MS3D. J Mol Biol 345:69–80

    Article  PubMed  CAS  Google Scholar 

  • Yusupov MM, Yusupova GZ, Baucom A, Lieberman K, Earnest TN, Cate JH, Noller HF (2001) Crystal structure of the ribosome at 5.5 A resolution. Science 292:883–896

    Article  PubMed  CAS  Google Scholar 

  • Yusupova GZ, Yusupov MM, Cate JH, Noller HF (2001) The path of messenger RNA through the ribosome. Cell 106:233–241

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Sergey Steinberg, Kevin Wilson and Steve Michnick for very stimulating discussions and for critical reading of this review. We are also grateful to Pascal Chartrand, Gerardo Ferbeyre, Nikolaus Heveker, Luis Rokeach and all the members of the Brakier-Gingras group for critical reading of this manuscript. Work from this laboratory that is cited herein was supported by the Canadian Institutes for Health Research.

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Authors and Affiliations

  1. Département de Biochimie, Université de Montréal, H3T 1J4, Montréal, Québec, Canada

    Léa Brakier-Gingras & Dominic Dulude

  2. Centre de Recherche, Hôpital Sainte-Justine, H3T 1C5, Montréal, QC, Canada

    Dominic Dulude

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  1. Léa Brakier-Gingras
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  2. Dominic Dulude
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Correspondence to Léa Brakier-Gingras .

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Editors and Affiliations

  1. Molecular Biology Program, University of Utah, N. 2030 E. 15, Salt Late City, 84112-5330, U.S.A.

    John F. Atkins

  2. Dept. Bioengineering, University of Utah, Salt Lake City, 84112, U.S.A.

    Raymond F. Gesteland

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Brakier-Gingras, L., Dulude, D. (2010). Programmed —1 Ribosomal Frameshift in the Human Immunodeficiency Virus of Type 1. In: Atkins, J., Gesteland, R. (eds) Recoding: Expansion of Decoding Rules Enriches Gene Expression. Nucleic Acids and Molecular Biology, vol 24. Springer, New York, NY. https://doi.org/10.1007/978-0-387-89382-2_8

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