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PMID: 19889724 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The 5'-untranslated region of the mouse mammary tumor virus mRNA exhibits cap-independent translation initiation.

Nucleic acids research ·Vol. 38 ·No. 2 ·2010-01-00 ·Pages 618-32

Vallejos M, Ramdohr P, Valiente-Echeverría F, Tapia K, Rodriguez FE, Lowy F, Huidobro-Toro JP, Dangerfield JA, López-Lastra M

Abstract

In this study, we demonstrate the identification of an internal ribosome entry site (IRES) within the 5'-untranslated region (5'-UTR) of the mouse mammary tumor virus (MMTV). The 5'-UTR of the full-length mRNA derived from the infectious, complete MMTV genome was cloned into a dual luciferase reporter construct containing an upstream Renilla luciferase gene (RLuc) and a downstream firefly luciferase gene (FLuc). In rabbit reticulocyte lysate, the MMTV 5'-UTR was capable of driving translation of the second cistron. In vitro translational activity from the MMTV 5'-UTR was resistant to the addition of m(7)GpppG cap-analog and cleavage of eIF4G by foot-and-mouth disease virus (FMDV) L-protease. IRES activity was also demonstrated in the Xenopus laevis oocyte by micro-injection of capped and polyadenylated bicistronic RNAs harboring the MMTV-5'-UTR. Finally, transfection assays showed that the MMTV-IRES exhibits cell type-dependent translational activity, suggesting a requirement for as yet unidentified cellular factors for its optimal function.

MeSH Terms
5' Untranslated Regions Animals Cell Line Humans Luciferases, Firefly/analysis,genetics Mammary Tumor Virus, Mouse/genetics Nucleocytoplasmic Transport Proteins/metabolism Oocytes/metabolism Peptide Chain Initiation, Translational Plasmids/genetics Promoter Regions, Genetic RNA Caps/antagonists & inhibitors RNA, Messenger/chemistry RNA, Viral/chemistry Rabbits Xenopus laevis rev Gene Products, Human Immunodeficiency Virus/metabolism
Chemicals
5' Untranslated Regions Nucleocytoplasmic Transport Proteins RNA Caps RNA, Messenger RNA, Viral rev Gene Products, Human Immunodeficiency Virus rev protein, Human Immunodeficiency Virus-1 Luciferases, Firefly
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Vallejos Maricarmen
Laboratorio de Virología Molecular, Instituto Milenio de Inmunología e Inmunoterapia, Centro de Investigaciones Médicas, Pontificia Universidad Católica de Chile, Marcoleta 391, Chile.
Ramdohr Pablo
Valiente-Echeverría Fernando
Tapia Karla
Rodriguez Felipe E
Lowy Fernando
Huidobro-Toro J Pablo
Dangerfield John A
López-Lastra Marcelo
References (71)
71 references, click to expand
  1. Oocyte expression with injection of purified T7 RNA polymerase.
    Methods Mol Biol. 2006;322:55-67 PMID: 16739716
  2. Cleavage of eIF4G by HIV-1 protease: effects on translation.
    FEBS Lett. 2003 Jan 2;533(1-3):89-94 PMID: 12505164
  3. Identification of the Rem-responsive element of mouse mammary tumor virus.
    Nucleic Acids Res. 2008 Nov;36(19):6284-94 PMID: 18835854
  4. Analysis of the c-myc IRES; a potential role for cell-type specific trans-acting factors and the nuclear compartment.
    Nucleic Acids Res. 2000 Feb 1;28(3):687-94 PMID: 10637319
  5. Proteolysis of human eukaryotic translation initiation factor eIF4GII, but not eIF4GI, coincides with the shutoff of host protein synthesis after poliovirus infection.
    Proc Natl Acad Sci U S A. 1998 Sep 15;95(19):11089-94 PMID: 9736694
  6. A guide to ions and RNA structure.
    RNA. 2004 Mar;10(3):335-43 PMID: 14970378
  7. elF4G and its proteolytic cleavage products: effect on initiation of protein synthesis from capped, uncapped, and IRES-containing mRNAs.
    RNA. 1997 Feb;3(2):186-96 PMID: 9042945
  8. SOME POSSIBLE EFFECTS OF NURSING ON THE MAMMARY GLAND TUMOR INCIDENCE IN MICE.
    Science. 1936 Aug 14;84(2172):162 PMID: 17793252
  9. Regulation of gene expression by internal ribosome entry sites or cryptic promoters: the eIF4G story.
    Mol Cell Biol. 2002 Nov;22(21):7372-84 PMID: 12370285
  10. The ins and outs of HIV Rev.
    Arch Biochem Biophys. 1999 May 15;365(2):186-91 PMID: 10328811
  11. Hijacking the translation apparatus by RNA viruses.
    J Cell Biol. 2002 Aug 5;158(3):395-9 PMID: 12163463
  12. The eukaryotic translation initiation factor 4GI is cleaved by different retroviral proteases.
    J Virol. 2003 Dec;77(23):12392-400 PMID: 14610163
  13. Genomic determinants of the efficiency of internal ribosomal entry sites of viral and cellular origin.
    Nucleic Acids Res. 2008 Dec;36(21):6918-25 PMID: 18978018
  14. Mouse mammary tumor virus infects human cells.
    Cancer Res. 2005 Aug 1;65(15):6651-9 PMID: 16061645
  15. 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
  16. Suppression of cap-dependent translation in mitosis.
    Genes Dev. 2001 Aug 15;15(16):2083-93 PMID: 11511540
  17. Differences in potency and efficacy of a series of phenylisopropylamine/phenylethylamine pairs at 5-HT(2A) and 5-HT(2C) receptors.
    Br J Pharmacol. 2002 Jun;136(4):510-9 PMID: 12055129
  18. Sequences homologous to the mouse mammary tumor virus env gene in human breast carcinoma correlate with overexpression of laminin receptor.
    Clin Cancer Res. 1999 Aug;5(8):2108-11 PMID: 10473094
  19. The human immunodeficiency virus type 1 gag gene encodes an internal ribosome entry site.
    J Virol. 2001 Jan;75(1):181-91 PMID: 11119587
  20. Translational control of retroviruses.
    Nat Rev Microbiol. 2007 Feb;5(2):128-40 PMID: 17224922
  21. Rev: beyond nuclear export.
    J Gen Virol. 2009 Jun;90(Pt 6):1303-1318 PMID: 19321757
  22. Proteolytic cleavage of initiation factor eIF-4 gamma in the reticulocyte lysate inhibits translation of capped mRNAs but enhances that of uncapped mRNAs.
    Nucleic Acids Res. 1995 Feb 11;23(3):334-40 PMID: 7885827
  23. HIV-1 Rev can specifically interact with MMTV RNA and upregulate gene expression.
    Gene. 2005 Sep 26;358:17-30 PMID: 16023306
  24. The C-terminal domain of eukaryotic protein synthesis initiation factor (eIF) 4G is sufficient to support cap-independent translation in the absence of eIF4E.
    EMBO J. 1996 Mar 15;15(6):1371-82 PMID: 8635470
  25. The two species of the foot-and-mouth disease virus leader protein, expressed individually, exhibit the same activities.
    Virology. 1993 May;194(1):355-9 PMID: 8386879
  26. Detection of mammary tumor virus env gene-like sequences in human breast cancer.
    Cancer Res. 1995 Nov 15;55(22):5173-9 PMID: 7585568
  27. Cap-independent translation initiation in Xenopus oocytes.
    Nucleic Acids Res. 1997 Jan 15;25(2):395-402 PMID: 9016570
  28. A role for Rev in the association of HIV-1 gag mRNA with cytoskeletal beta-actin and viral protein expression.
    Biochimie. 1996;78(11-12):1075-80 PMID: 9150887
  29. Production of mouse mammary tumor virus upon transfection of a recombinant proviral DNA into cultured cells.
    Virology. 1985 Jul 15;144(1):101-14 PMID: 2998037
  30. Analysis of natural variants of the hepatitis C virus internal ribosome entry site reveals that primary sequence plays a key role in cap-independent translation.
    Nucleic Acids Res. 2009 Feb;37(3):957-71 PMID: 19106142
  31. Aberrant translational control of the c-myc gene in multiple myeloma.
    Oncogene. 1996 Aug 1;13(3):505-13 PMID: 8760292
  32. The Elav-like protein HuR exerts translational control of viral internal ribosome entry sites.
    Virology. 2009 Sep 30;392(2):178-85 PMID: 19647848
  33. HIV-1 protease cleaves eukaryotic initiation factor 4G and inhibits cap-dependent translation.
    Proc Natl Acad Sci U S A. 2001 Nov 6;98(23):12966-71 PMID: 11606767
  34. 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
  35. Rapid spread of mouse mammary tumor virus in cultured human breast cells.
    Retrovirology. 2007 Oct 11;4:73 PMID: 17931409
  36. Regulation of translation initiation in eukaryotes: mechanisms and biological targets.
    Cell. 2009 Feb 20;136(4):731-45 PMID: 19239892
  37. Naturally occurring dicistronic cricket paralysis virus RNA is regulated by two internal ribosome entry sites.
    Mol Cell Biol. 2000 Jul;20(14):4990-9 PMID: 10866656
  38. Essential role for eIF4GI overexpression in the pathogenesis of inflammatory breast cancer.
    Nat Cell Biol. 2009 Jul;11(7):903-8 PMID: 19525934
  39. Efficient cleavage of p220 by poliovirus 2Apro expression in mammalian cells: effects on vaccinia virus.
    Biochem Biophys Res Commun. 1995 Oct 24;215(3):928-36 PMID: 7488063
  40. Rev is necessary for translation but not cytoplasmic accumulation of HIV-1 vif, vpr, and env/vpu 2 RNAs.
    Genes Dev. 1991 May;5(5):808-19 PMID: 1827422
  41. In vitro cleavage of eIF4GI but not eIF4GII by HIV-1 protease and its effects on translation in the rabbit reticulocyte lysate system.
    J Mol Biol. 2002 Apr 19;318(1):9-20 PMID: 12054764
  42. A segment of the 5' nontranslated region of encephalomyocarditis virus RNA directs internal entry of ribosomes during in vitro translation.
    J Virol. 1988 Aug;62(8):2636-43 PMID: 2839690
  43. Members of the poly (rC) binding protein family stimulate the activity of the c-myc internal ribosome entry segment in vitro and in vivo.
    Oncogene. 2003 Sep 11;22(39):8012-20 PMID: 12970749
  44. Mouse mammary tumor virus encodes a self-regulatory RNA export protein and is a complex retrovirus.
    J Virol. 2005 Dec;79(23):14737-47 PMID: 16282474
  45. Picornavirus RNA translation: roles for cellular proteins.
    Trends Microbiol. 2000 Jul;8(7):330-5 PMID: 10878768
  46. Rev binds specifically to a purine loop in the SL1 region of the HIV-1 leader RNA.
    J Biol Chem. 2003 Oct 10;278(41):40385-91 PMID: 12851400
  47. A novel, mouse mammary tumor virus encoded protein with Rev-like properties.
    Virology. 2005 Jun 20;337(1):1-6 PMID: 15914215
  48. Eukaryotic translation initiation factor 4E availability controls the switch between cap-dependent and internal ribosomal entry site-mediated translation.
    Mol Cell Biol. 2005 Dec;25(23):10556-65 PMID: 16287867
  49. Cell cycle arrest in G2 induces human immunodeficiency virus type 1 transcriptional activation through histone acetylation and recruitment of CBP, NF-kappaB, and c-Jun to the long terminal repeat promoter.
    J Virol. 2004 Nov;78(22):12198-206 PMID: 15507606
  50. Construction of mutant and chimeric genes using the polymerase chain reaction.
    Nucleic Acids Res. 1989 Jan 25;17(2):723-33 PMID: 2915928
  51. Mouse mammary tumour virus-like virus (MMTV-LV) is present within the liver in a wide range of hepatic disorders and unrelated to nuclear p53 expression or hepatocarcinogenesis.
    J Hepatol. 2009 Mar;50(3):548-54 PMID: 19168254
  52. Endogenous mammary tumour virus DNA varies among wild mice and segregates during inbreeding.
    Nature. 1979 Mar 29;278(5703):418-23 PMID: 221817
  53. Rev regulates translation of human immunodeficiency virus type 1 RNAs.
    J Gen Virol. 2009 May;90(Pt 5):1141-1147 PMID: 19264599
  54. The possible involvement of virus in breast cancer.
    J Cancer Res Clin Oncol. 2009 Mar;135(3):329-37 PMID: 19009309
  55. Characterization of human MMTV-like (HML) elements similar to a sequence that was highly expressed in a human breast cancer: further definition of the HML-6 group.
    Virology. 1999 Mar 30;256(1):22-35 PMID: 10087223
  56. A hypoxia-controlled cap-dependent to cap-independent translation switch in breast cancer.
    Mol Cell. 2007 Nov 9;28(3):501-12 PMID: 17996713
  57. Mapping of functional domains in eukaryotic protein synthesis initiation factor 4G (eIF4G) with picornaviral proteases. Implications for cap-dependent and cap-independent translational initiation.
    J Biol Chem. 1995 Sep 15;270(37):21975-83 PMID: 7665619
  58. Exploring RNA virus replication in Xenopus oocytes.
    Methods Mol Biol. 2006;322:367-78 PMID: 16739737
  59. Cap-dependent and cap-independent translation: operational distinctions and mechanistic interpretations.
    Curr Top Microbiol Immunol. 1995;203:1-29 PMID: 7555086
  60. Protein synthesis in eukaryotes: the growing biological relevance of cap-independent translation initiation.
    Biol Res. 2005;38(2-3):121-46 PMID: 16238092
  61. eIF4E, the mRNA cap-binding protein: from basic discovery to translational research.
    Biochem Cell Biol. 2008 Apr;86(2):178-83 PMID: 18443631
  62. Internal initiation of translation of eukaryotic mRNA directed by a sequence derived from poliovirus RNA.
    Nature. 1988 Jul 28;334(6180):320-5 PMID: 2839775
  63. MMTV-induced mutations in mouse mammary tumors: their potential relevance to human breast cancer.
    Breast Cancer Res Treat. 1996;39(1):33-44 PMID: 8738604
  64. Rev and Rex proteins of human complex retroviruses function with the MMTV Rem-responsive element.
    Retrovirology. 2009 Feb 03;6:10 PMID: 19192308
  65. Replication of poliovirus in Xenopus oocytes requires two human factors.
    EMBO J. 1996 Nov 1;15(21):5988-98 PMID: 8918476
  66. A mutation in the c-myc-IRES leads to enhanced internal ribosome entry in multiple myeloma: a novel mechanism of oncogene de-regulation.
    Oncogene. 2000 Sep 7;19(38):4437-40 PMID: 10980620
  67. 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
  68. The Rev protein of human immunodeficiency virus type 1 promotes polysomal association and translation of gag/pol and vpu/env mRNAs.
    Mol Cell Biol. 1992 Mar;12(3):1375-86 PMID: 1545819
  69. An internal ribosome entry site promotes translation of a novel SIV Pr55(Gag) isoform.
    Virology. 2006 Jun 5;349(2):325-34 PMID: 16494914
  70. Lentiviral RNAs can use different mechanisms for translation initiation.
    Biochem Soc Trans. 2008 Aug;36(Pt 4):690-3 PMID: 18631141
  71. The HIV-1 rev trans-activator acts through a structured target sequence to activate nuclear export of unspliced viral mRNA.
    Nature. 1989 Mar 16;338(6212):254-7 PMID: 2784194
Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkp890
Published
2010-01-00
Epub
2009-00-04
Pages
618-32
Language
English
Region
England
NLM ID
0411011
PMCID
PMC2811009
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/gkp890 PMC Full Text View journal details
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