Home LiteratureArticle Details
PMID: 19969542 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A new type of IRES within gag coding region recruits three initiation complexes on HIV-2 genomic RNA.

Nucleic acids research ·Vol. 38 ·No. 4 ·2010-03-00 ·Pages 1367-81

Weill L, James L, Ulryck N, Chamond N, Herbreteau CH, Ohlmann T, Sargueil B

Abstract

Genomic RNA of primate lentiviruses serves both as an mRNA that encodes Gag and Gag-Pol polyproteins and as a propagated genome. Translation of this RNA is initiated by standard cap dependant mechanism or by internal entry of the ribosome. Two regions of the genomic RNA are able to attract initiation complexes, the 5' untranslated region and the gag coding region itself. Relying on probing data and a phylogenetic study, we have modelled the secondary structure of HIV-1, HIV-2 and SIV(Mac) coding region. This approach brings to light conserved secondary-structure elements that were shown by mutations to be required for internal entry of the ribosome. No structural homologies with other described viral or cellular IRES can be identified and lentiviral IRESes show many peculiar properties. Most notably, the IRES present in HIV-2 gag coding region is endowed with the unique ability to recruit up to three initiation complexes on a single RNA molecule. The structural and functional properties of gag coding sequence define a new type of IRES. Although its precise role is unknown, the conservation of the IRES among fast evolving lentiviruses suggests an important physiological role.

MeSH Terms
Ecthyma, Contagious Eukaryotic Initiation Factors/metabolism Genome, Viral HIV-1/genetics HIV-2/genetics Mutagenesis, Site-Directed Nucleic Acid Conformation Peptide Chain Initiation, Translational RNA, Viral/chemistry,metabolism Simian Immunodeficiency Virus/genetics gag Gene Products, Human Immunodeficiency Virus/genetics
Chemicals
Eukaryotic Initiation Factors RNA, Viral gag Gene Products, Human Immunodeficiency Virus
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Weill Laure
CNRS UMR 8015, Laboratoire de cristallographie et RMN Biologique, Université Paris Descartes, 4 avenue de l'Observatoire, 75270 Paris Cedex 06, France.
James Laurie
Ulryck Nathalie
Chamond Nathalie
Herbreteau Cecile H
Ohlmann Theophile
Sargueil Bruno
References (53)
53 references, click to expand
  1. HIV-1 RNA packaging.
    Adv Pharmacol. 2007;55:1-32 PMID: 17586311
  2. The human immunodeficiency virus type 1 5' packaging signal structure affects translation but does not function as an internal ribosome entry site structure.
    J Virol. 1996 Feb;70(2):944-51 PMID: 8551634
  3. The role of 5'-leader length, secondary structure and PABP concentration on cap and poly(A) tail function during translation in Xenopus oocytes.
    Nucleic Acids Res. 2000 Aug 1;28(15):2943-53 PMID: 10908358
  4. The human immunodeficiency virus type 1 gag gene encodes an internal ribosome entry site.
    J Virol. 2001 Jan;75(1):181-91 PMID: 11119587
  5. Probing RNA structure and RNA-ligand complexes with chemical probes.
    Methods Enzymol. 2000;318:3-21 PMID: 10889976
  6. Human immunodeficiency virus types 1 and 2 differ in the predominant mechanism used for selection of genomic RNA for encapsidation.
    J Virol. 1999 Apr;73(4):3023-31 PMID: 10074152
  7. In vitro expression of the HIV-2 genomic RNA is controlled by three distinct internal ribosome entry segments that are regulated by the HIV protease and the Gag polyprotein.
    RNA. 2008 Jul;14(7):1443-55 PMID: 18495939
  8. A novel long distance base-pairing interaction in human immunodeficiency virus type 1 RNA occludes the Gag start codon.
    J Biol Chem. 2003 Mar 28;278(13):11601-11 PMID: 12458192
  9. Translation initiation at non-AUG triplets in mammalian cells.
    J Biol Chem. 1989 Mar 25;264(9):5031-5 PMID: 2538469
  10. Recognition of AUG and alternative initiator codons is augmented by G in position +4 but is not generally affected by the nucleotides in positions +5 and +6.
    EMBO J. 1997 May 1;16(9):2482-92 PMID: 9171361
  11. The roles of individual eukaryotic translation initiation factors in ribosomal scanning and initiation codon selection.
    Genes Dev. 2002 Nov 15;16(22):2906-22 PMID: 12435632
  12. Structural basis for ribosome recruitment and manipulation by a viral IRES RNA.
    Science. 2006 Dec 1;314(5804):1450-4 PMID: 17124290
  13. Generation of protein isoform diversity by alternative initiation of translation at non-AUG codons.
    Biol Cell. 2003 May-Jun;95(3-4):169-78 PMID: 12867081
  14. The pathway of hepatitis C virus mRNA recruitment to the human ribosome.
    Nat Struct Mol Biol. 2009 Apr;16(4):397-404 PMID: 19287397
  15. Analysis of 40 S and 80 S complexes with mRNA as measured by sucrose density gradients and primer extension inhibition.
    J Biol Chem. 1992 Jan 25;267(3):1554-62 PMID: 1730701
  16. Specific functional interactions of nucleotides at key -3 and +4 positions flanking the initiation codon with components of the mammalian 48S translation initiation complex.
    Genes Dev. 2006 Mar 1;20(5):624-36 PMID: 16510876
  17. Viral IRES RNA structures and ribosome interactions.
    Trends Biochem Sci. 2008 Jun;33(6):274-83 PMID: 18468443
  18. The HIV-1 leader RNA conformational switch regulates RNA dimerization but does not regulate mRNA translation.
    Biochemistry. 2005 Jun 28;44(25):9058-66 PMID: 15966729
  19. HIV-2 genomic RNA contains a novel type of IRES located downstream of its initiation codon.
    Nat Struct Mol Biol. 2005 Nov;12(11):1001-7 PMID: 16244661
  20. The fidelity of translation initiation: reciprocal activities of eIF1, IF3 and YciH.
    EMBO J. 2006 Jan 11;25(1):196-210 PMID: 16362046
  21. Translational control of retroviruses.
    Nat Rev Microbiol. 2007 Feb;5(2):128-40 PMID: 17224922
  22. Conversion of 48S translation preinitiation complexes into 80S initiation complexes as revealed by toeprinting.
    FEBS Lett. 2003 Jan 2;533(1-3):99-104 PMID: 12505166
  23. An atypical IRES within the 5' UTR of a dicistrovirus genome.
    Virus Res. 2009 Feb;139(2):157-65 PMID: 18755228
  24. Retrovirus translation initiation: Issues and hypotheses derived from study of HIV-1.
    Curr HIV Res. 2006 Apr;4(2):131-9 PMID: 16611053
  25. A 5'UTR-spliced mRNA isoform is specialized for enhanced HIV-2 gag translation.
    J Mol Biol. 2009 Aug 14;391(2):426-37 PMID: 19559029
  26. In vitro evidence for a long range pseudoknot in the 5'-untranslated and matrix coding regions of HIV-1 genomic RNA.
    J Biol Chem. 2002 Feb 22;277(8):5995-6004 PMID: 11744696
  27. Cooperative and specific binding of Vif to the 5' region of HIV-1 genomic RNA.
    J Mol Biol. 2005 Nov 18;354(1):55-72 PMID: 16236319
  28. An internal ribosome entry segment promotes translation of the simian immunodeficiency virus genomic RNA.
    J Biol Chem. 2000 Apr 21;275(16):11899-906 PMID: 10766817
  29. Primer extension analysis of eukaryotic ribosome-mRNA complexes.
    Nucleic Acids Res. 1998 Nov 1;26(21):4853-9 PMID: 9776744
  30. Circumstances and mechanisms of inhibition of translation by secondary structure in eucaryotic mRNAs.
    Mol Cell Biol. 1989 Nov;9(11):5134-42 PMID: 2601712
  31. HIV-1 reverse transcription: close encounters between the viral genome and a cellular tRNA.
    Adv Pharmacol. 2007;55:99-135 PMID: 17586313
  32. Translation is not required To generate virion precursor RNA in human immunodeficiency virus type 1-infected T cells.
    J Virol. 2000 Dec;74(24):11531-7 PMID: 11090150
  33. Destiny of unspliced retroviral RNA: ribosome and/or virion?
    J Virol. 2002 Apr;76(7):3089-94 PMID: 11884533
  34. The structural biology of HIV assembly.
    Curr Opin Struct Biol. 2008 Apr;18(2):203-17 PMID: 18406133
  35. Mfold web server for nucleic acid folding and hybridization prediction.
    Nucleic Acids Res. 2003 Jul 1;31(13):3406-15 PMID: 12824337
  36. RNA secondary structure of the feline immunodeficiency virus 5'UTR and Gag coding region.
    Nucleic Acids Res. 2008 Aug;36(14):4653-66 PMID: 18625613
  37. A cross-kingdom internal ribosome entry site reveals a simplified mode of internal ribosome entry.
    Mol Cell Biol. 2005 Sep;25(17):7879-88 PMID: 16107731
  38. Transcription of HIV: Tat and cellular chromatin.
    Adv Pharmacol. 2007;55:137-59 PMID: 17586314
  39. Analysis of the functional role of a G.A sheared base pair by in vitro genetics.
    J Biol Chem. 2000 Oct 13;275(41):32157-66 PMID: 10906144
  40. RNA structure modulates splicing efficiency at the human immunodeficiency virus type 1 major splice donor.
    J Virol. 2008 Mar;82(6):3090-8 PMID: 18160437
  41. In vitro selection of second site revertants analysis of the hairpin ribozyme active site.
    J Biol Chem. 2003 Dec 26;278(52):52783-91 PMID: 14555657
  42. Initiation of protein synthesis from the A site of the ribosome.
    Cell. 2000 Aug 18;102(4):511-20 PMID: 10966112
  43. Dimerization of retroviral RNA genomes: an inseparable pair.
    Nat Rev Microbiol. 2004 Jun;2(6):461-72 PMID: 15152202
  44. Selection and evolution of NTP-specific aptamers.
    Nucleic Acids Res. 2004 Sep 27;32(17):5045-58 PMID: 15452272
  45. High-throughput SHAPE analysis reveals structures in HIV-1 genomic RNA strongly conserved across distinct biological states.
    PLoS Biol. 2008 Apr 29;6(4):e96 PMID: 18447581
  46. Structure of the ribosome-bound cricket paralysis virus IRES RNA.
    Nat Struct Mol Biol. 2006 Dec;13(12):1092-6 PMID: 17115051
  47. RNA interactions in the 5' region of the HIV-1 genome.
    J Mol Biol. 2004 Feb 13;336(2):369-79 PMID: 14757051
  48. 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. 2003 Apr;77(7):3939-49 PMID: 12634354
  49. Hepatitis C virus IRES RNA-induced changes in the conformation of the 40s ribosomal subunit.
    Science. 2001 Mar 9;291(5510):1959-62 PMID: 11239155
  50. An internal ribosome entry site promotes translation of a novel SIV Pr55(Gag) isoform.
    Virology. 2006 Jun 5;349(2):325-34 PMID: 16494914
  51. Lentiviral RNAs can use different mechanisms for translation initiation.
    Biochem Soc Trans. 2008 Aug;36(Pt 4):690-3 PMID: 18631141
  52. Influence of mRNA secondary structure on binding and migration of 40S ribosomal subunits.
    Cell. 1980 Jan;19(1):79-90 PMID: 7357609
  53. Differential factor requirement to assemble translation initiation complexes at the alternative start codons of foot-and-mouth disease virus RNA.
    RNA. 2007 Aug;13(8):1366-74 PMID: 17592045
Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkp1109
Published
2010-03-00
Epub
2009-00-06
Pages
1367-81
Language
English
Region
England
NLM ID
0411011
PMCID
PMC2831325
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/gkp1109 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2