Home LiteratureArticle Details
PMID: 1729599 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Mechanism of translation of monocistronic and multicistronic human immunodeficiency virus type 1 mRNAs.

Molecular and cellular biology ·Vol. 12 ·No. 1 ·1992-01-00 ·Pages 207-19

Schwartz S, Felber BK, Pavlakis GN

Abstract

We have used a panel of cDNA clones expressing wild-type and mutant human immunodeficiency virus type 1 (HIV-1) mRNAs to study translation of these mRNAs in eucaryotic cells. The tat open reading frame (ORF) has a strong signal for translation initiation, while rev and vpu ORFs have weaker signals. The expression of downstream ORFs is inhibited in mRNAs that contain the tat ORF as the first ORF. In contrast, downstream ORFs are expressed efficiently from mRNAs that have rev or vpu as the first ORF. All env mRNAs contain the upstream vpu ORF. Expression of HIV-1 Env protein requires a weak vpu AUG, which allows leaky scanning to occur, thereby allowing ribosomes access to the downstream env ORF. We concluded that HIV-1 mRNAs are translated by the scanning mechanism and that expression of more than one protein from each mRNA was caused by leaky scanning at the first AUG of the mRNA.

Related Genes
MeSH Terms
Base Sequence DNA, Viral Gene Expression Regulation, Viral Genes, rev Genes, tat HIV-1/genetics Molecular Sequence Data Mutation Open Reading Frames Precipitin Tests Protein Biosynthesis RNA Splicing RNA, Messenger/metabolism RNA, Viral/metabolism
Chemicals
DNA, Viral RNA, Messenger RNA, Viral
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Schwartz S
Human Retrovirus Section, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201.
Felber B K
Pavlakis G N
References (83)
83 references, click to expand
  1. Multiple cis-acting elements modulate the translational efficiency of GCN4 mRNA in yeast.
    Proc Natl Acad Sci U S A. 1986 Jul;83(13):4849-53 PMID: 3088566
  2. Evidence that the GCN2 protein kinase regulates reinitiation by yeast ribosomes.
    EMBO J. 1988 Nov;7(11):3547-51 PMID: 3061799
  3. Identification of a protein encoded by the vpu gene of HIV-1.
    Nature. 1988 Aug 11;334(6182):532-4 PMID: 3043230
  4. Functional role of human immunodeficiency virus type 1 vpu.
    Proc Natl Acad Sci U S A. 1989 Jul;86(13):5163-7 PMID: 2472639
  5. Synthesis and encapsidation of duck hepatitis B virus reverse transcriptase do not require formation of core-polymerase fusion proteins.
    Cell. 1989 Jan 13;56(1):85-92 PMID: 2463093
  6. Biosynthesis of the reverse transcriptase of hepatitis B viruses involves de novo translational initiation not ribosomal frameshifting.
    Nature. 1989 Jan 26;337(6205):364-8 PMID: 2463489
  7. Isolation of RNA for dot hybridization by heparin-DNase I treatment of whole cell lysate.
    Anal Biochem. 1987 Aug 15;165(1):20-7 PMID: 2446524
  8. Complete nucleotide sequence of the AIDS virus, HTLV-III.
    Nature. 1985 Jan 24-30;313(6000):277-84 PMID: 2578615
  9. Structure of simian immunodeficiency virus regulatory genes.
    Proc Natl Acad Sci U S A. 1989 Jul;86(13):4813-7 PMID: 2544874
  10. Internal binding of eucaryotic ribosomes on poliovirus RNA: translation in HeLa cell extracts.
    J Virol. 1989 Jan;63(1):441-4 PMID: 2535747
  11. Functional comparison of the Rev trans-activators encoded by different primate immunodeficiency virus species.
    Proc Natl Acad Sci U S A. 1989 Nov;86(21):8222-6 PMID: 2682638
  12. Alternatives for the initiation of translation.
    Trends Biochem Sci. 1989 Jun;14(6):219-22 PMID: 2669238
  13. Sequences that surround the stop codons of upstream open reading frames in GCN4 mRNA determine their distinct functions in translational control.
    Genes Dev. 1989 Aug;3(8):1217-25 PMID: 2676723
  14. rev protein of human immunodeficiency virus type 1 affects the stability and transport of the viral mRNA.
    Proc Natl Acad Sci U S A. 1989 Mar;86(5):1495-9 PMID: 2784208
  15. How 'hidden' reading frames are expressed.
    Trends Biochem Sci. 1989 May;14(5):165-7 PMID: 2773038
  16. The scanning model for translation: an update.
    J Cell Biol. 1989 Feb;108(2):229-41 PMID: 2645293
  17. Rev-induced modulation of Nef protein underlies temporal regulation of human immunodeficiency virus replication.
    Proc Natl Acad Sci U S A. 1989 Aug;86(16):6111-5 PMID: 2788283
  18. Molecular and biochemical analyses of human immunodeficiency virus type 1 vpu protein.
    J Virol. 1989 Sep;63(9):3784-91 PMID: 2788224
  19. The rev (trs/art) protein of human immunodeficiency virus type 1 affects viral mRNA and protein expression via a cis-acting sequence in the env region.
    J Virol. 1989 Mar;63(3):1265-74 PMID: 2783738
  20. A novel gene of HIV-1, vpu, and its 16-kilodalton product.
    Science. 1988 Sep 2;241(4870):1221-3 PMID: 3261888
  21. RNA translation. Picornaviruses break the rules.
    Nature. 1988 Jul 28;334(6180):292-3 PMID: 3393222
  22. Translational regulation of B19 parvovirus capsid protein production by multiple upstream AUG triplets.
    J Biol Chem. 1988 Aug 5;263(22):10922-6 PMID: 3392047
  23. Mutation of a termination codon affects src initiation.
    Mol Cell Biol. 1984 Sep;4(9):1738-46 PMID: 6092936
  24. An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs.
    Nucleic Acids Res. 1987 Oct 26;15(20):8125-48 PMID: 3313277
  25. A segment of GCN4 mRNA containing the upstream AUG codons confers translational control upon a heterologous yeast transcript.
    Proc Natl Acad Sci U S A. 1987 May;84(9):2863-7 PMID: 3554249
  26. Complete nucleotide sequences of functional clones of the virus associated with the acquired immunodeficiency syndrome, HTLV-III/LAV.
    Haematol Blood Transfus. 1987;31:404-6 PMID: 3443402
  27. HTLV-III expression and production involve complex regulation at the levels of splicing and translation of viral RNA.
    Cell. 1986 Sep 12;46(6):807-17 PMID: 3638988
  28. Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes.
    Cell. 1986 Jan 31;44(2):283-92 PMID: 3943125
  29. mRNA cap binding proteins: essential factors for initiating translation.
    Cell. 1985 Feb;40(2):223-4 PMID: 3967293
  30. Functional analysis of the internal translation initiation site of foot-and-mouth disease virus.
    J Virol. 1990 Oct;64(10):4625-31 PMID: 2168956
  31. Identification of a cis-acting element in human immunodeficiency virus type 2 (HIV-2) that is responsive to the HIV-1 rev and human T-cell leukemia virus types I and II rex proteins.
    J Virol. 1990 Apr;64(4):1690-7 PMID: 2157051
  32. Tat and Rev: positive regulators of HIV gene expression.
    AIDS. 1990 Jun;4(6):499-509 PMID: 2201316
  33. Function of the human immunodeficiency virus types 1 and 2 Rev proteins is dependent on their ability to interact with a structured region present in env gene mRNA.
    J Virol. 1990 Sep;64(9):4428-37 PMID: 2200888
  34. Feedback regulation of human immunodeficiency virus type 1 expression by the Rev protein.
    J Virol. 1990 Aug;64(8):3734-41 PMID: 2196381
  35. Structure and expression of tat-, rev-, and nef-specific transcripts of human immunodeficiency virus type 1 in infected lymphocytes and macrophages.
    J Virol. 1990 Jul;64(7):3391-8 PMID: 2191150
  36. A novel human immunodeficiency virus type 1 protein, tev, shares sequences with tat, env, and rev proteins.
    J Virol. 1990 Jun;64(6):2505-18 PMID: 2186172
  37. Identification of trans-dominant HIV-1 rev protein mutants by direct transfer of bacterially produced proteins into human cells.
    Nucleic Acids Res. 1990 Apr 25;18(8):2037-44 PMID: 2186373
  38. A tripartite HIV-1 tat-env-rev fusion protein.
    EMBO J. 1990 Mar;9(3):965-70 PMID: 2178928
  39. Simian immunodeficiency virus displays complex patterns of RNA splicing.
    J Virol. 1990 Sep;64(9):4207-16 PMID: 2384918
  40. Alternative splice acceptor utilization during human immunodeficiency virus type 1 infection of cultured cells.
    J Virol. 1990 Sep;64(9):4093-8 PMID: 2384914
  41. Cloning and functional analysis of multiply spliced mRNA species of human immunodeficiency virus type 1.
    J Virol. 1990 Jun;64(6):2519-29 PMID: 2335812
  42. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells.
    Mol Cell Biol. 1982 Sep;2(9):1044-51 PMID: 6960240
  43. Initiation of translation at internal AUG codons in mammalian cells.
    Nature. 1984 May 3-9;309(5963):82-5 PMID: 6717585
  44. Capping of eucaryotic mRNAs.
    Cell. 1976 Dec;9(4 PT 2):645-53 PMID: 1017010
  45. A new technique for the assay of infectivity of human adenovirus 5 DNA.
    Virology. 1973 Apr;52(2):456-67 PMID: 4705382
  46. Initiation of translation of the cauliflower mosaic virus genome from a polycistronic mRNA: evidence from deletion mutagenesis.
    EMBO J. 1984 Dec 1;3(12):2731-6 PMID: 16453575
  47. Conservative mutations in the putative metal-binding region of human immunodeficiency virus tat disrupt virus replication.
    AIDS Res Hum Retroviruses. 1990 Nov;6(11):1257-63 PMID: 2078407
  48. Distinct RNA sequences in the gag region of human immunodeficiency virus type 1 decrease RNA stability and inhibit expression in the absence of Rev protein.
    J Virol. 1992 Jan;66(1):150-9 PMID: 1727477
  49. Expression of human immunodeficiency virus type 1 vif and vpr mRNAs is Rev-dependent and regulated by splicing.
    Virology. 1991 Aug;183(2):677-86 PMID: 1830183
  50. Cap-independent translation of encephalomyocarditis virus RNA: structural elements of the internal ribosomal entry site and involvement of a cellular 57-kD RNA-binding protein.
    Genes Dev. 1990 Sep;4(9):1560-72 PMID: 2174810
  51. Initiation of encephalomyocarditis virus RNA translation: the authentic initiation site is not selected by a scanning mechanism.
    EMBO J. 1990 Nov;9(11):3753-9 PMID: 2170120
  52. Different sites of interaction for Rev, Tev, and Rex proteins within the Rev-responsive element of human immunodeficiency virus type 1.
    J Virol. 1990 Dec;64(12):6010-7 PMID: 2243384
  53. Env and Vpu proteins of human immunodeficiency virus type 1 are produced from multiple bicistronic mRNAs.
    J Virol. 1990 Nov;64(11):5448-56 PMID: 2214021
  54. The leading sequence of caulimovirus large RNA can be folded into a large stem-loop structure.
    Nucleic Acids Res. 1988 Sep 12;16(17):8377-90 PMID: 3419922
  55. Scanning independent ribosomal initiation of the Sendai virus X protein.
    EMBO J. 1988 Sep;7(9):2869-74 PMID: 2846286
  56. Multiple upstream AUG codons mediate translational control of GCN4.
    Cell. 1986 Apr 25;45(2):201-7 PMID: 3516411
  57. Translational regulation of SV40 early mRNA defines a new viral protein.
    Cell. 1987 Feb 27;48(4):639-45 PMID: 3028644
  58. Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia.
    Science. 1985 Dec 20;230(4732):1350-4 PMID: 2999980
  59. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase.
    Science. 1988 Jan 29;239(4839):487-91 PMID: 2448875
  60. Secreted placental alkaline phosphatase: a powerful new quantitative indicator of gene expression in eukaryotic cells.
    Gene. 1988 Jun 15;66(1):1-10 PMID: 3417148
  61. Initiation of protein synthesis by internal entry of ribosomes into the 5' nontranslated region of encephalomyocarditis virus RNA in vivo.
    J Virol. 1989 Apr;63(4):1651-60 PMID: 2538648
  62. Translation in mammalian cells of a gene linked to the poliovirus 5' noncoding region.
    Science. 1988 Jul 22;241(4864):445-8 PMID: 2839901
  63. Bifunctional messenger RNAs in eukaryotes.
    Cell. 1986 Nov 21;47(4):481-3 PMID: 3779834
  64. Site-directed mutagenesis of two trans-regulatory genes (tat-III,trs) of HIV-1.
    Science. 1988 Feb 19;239(4842):910-3 PMID: 3277284
  65. Effects of intercistronic length on the efficiency of reinitiation by eucaryotic ribosomes.
    Mol Cell Biol. 1987 Oct;7(10):3438-45 PMID: 3683388
  66. The pX protein of HTLV-I is a transcriptional activator of its long terminal repeats.
    Science. 1985 Aug 16;229(4714):675-9 PMID: 2992082
  67. The specificity of the human immunodeficiency virus type 2 transactivator is different from that of human immunodeficiency virus type 1.
    EMBO J. 1987 Dec 1;6(12):3755-60 PMID: 2828036
  68. Cap-independent translation of poliovirus mRNA is conferred by sequence elements within the 5' noncoding region.
    Mol Cell Biol. 1988 Mar;8(3):1103-12 PMID: 2835660
  69. An RNA sequence of hundreds of nucleotides at the 5' end of poliovirus RNA is involved in allowing viral protein synthesis.
    J Virol. 1988 Jul;62(7):2291-9 PMID: 2836612
  70. 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
  71. Functional comparison of transactivation by simian immunodeficiency virus from rhesus macaques and human immunodeficiency virus type 1.
    J Virol. 1988 Dec;62(12):4523-32 PMID: 2846868
  72. Regulation of protein synthesis in virus-infected animal cells.
    Adv Virus Res. 1986;31:229-92 PMID: 3019107
  73. Internal initiation of translation on the vesicular stomatitis virus phosphoprotein mRNA yields a second protein.
    J Virol. 1986 Jun;58(3):797-804 PMID: 3009888
  74. Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone.
    J Virol. 1986 Aug;59(2):284-91 PMID: 3016298
  75. A second post-transcriptional trans-activator gene required for HTLV-III replication.
    Nature. 1986 May 22-28;321(6068):412-7 PMID: 3012355
  76. Termination-reinitiation occurs in the translation of mammalian cell mRNAs.
    Mol Cell Biol. 1986 Jul;6(7):2695-703 PMID: 3023945
  77. Three novel genes of human T-lymphotropic virus type III: immune reactivity of their products with sera from acquired immune deficiency syndrome patients.
    Proc Natl Acad Sci U S A. 1986 Apr;83(7):2209-13 PMID: 3008154
  78. New human and simian HIV-related retroviruses possess functional transactivator (tat) gene.
    Nature. 1987 Aug 6-12;328(6130):548-50 PMID: 3039372
  79. Selective translation initiation on bicistronic simian virus 40 late mRNA.
    J Virol. 1987 Jul;61(7):2331-5 PMID: 3035232
  80. Genome organization and transactivation of the human immunodeficiency virus type 2.
    Nature. 1987 Apr 16-22;326(6114):662-9 PMID: 3031510
  81. Effects of cDNA hybridization on translation of encephalomyocarditis virus RNA.
    J Virol. 1987 Jun;61(6):2033-7 PMID: 3033330
  82. Complete nucleotide sequences of functional clones of the AIDS virus.
    AIDS Res Hum Retroviruses. 1987 Spring;3(1):57-69 PMID: 3040055
  83. Nucleic acid structure and expression of the human AIDS/lymphadenopathy retrovirus.
    Nature. 1985 Feb 7-13;313(6002):450-8 PMID: 2982104
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
Published
1992-01-00
Pages
207-19
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC364085
Subset
IM
Grants
NCI NIH HHS · N01-CO-74101 · United States
Databases
GENBANK
K03455
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: [email protected]