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PMID: 3181141 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Mutational analysis of the 5' non-coding region of human immunodeficiency virus type 1: effects of secondary structure on translation.

The EMBO journal ·Vol. 7 ·No. 9 ·1988-09-00 ·Pages 2831-7

Parkin NT, Cohen EA, Darveau A, Rosen C, Haseltine W, Sonenberg N

Abstract

The first 111 nt from the 5' end of human immunodeficiency virus type 1 (HIV-1) mRNAs are shown to have a strong inhibitory effect on the translation of mRNA in in vitro translation extracts as well as in Xenopus oocytes. Mutations in the sequence of the 5' untranslated region (UTR) designed to disrupt predicted secondary structure of this region relieve the inhibition. Inhibition is restored by mutations that reconstruct the predicted secondary structure. The accessibility of the 5'-terminal cap structure was also found to be increased by some of these mutations. We conclude that secondary structure in the 5' UTR of HIV-1 mRNAs and resultant inaccessibility of the cap structure is responsible for the inhibition of translation. The implications of these findings for the understanding of the life cycle of HIV-1 are discussed.

MeSH Terms
Animals Chloramphenicol O-Acetyltransferase/biosynthesis,genetics Female HIV-1/genetics Humans Microinjections Mutation Nucleic Acid Conformation Oocytes Plasmids Protein Biosynthesis RNA, Messenger/analysis,genetics RNA, Viral/analysis,genetics Transcription, Genetic Xenopus laevis
Chemicals
RNA, Messenger RNA, Viral Chloramphenicol O-Acetyltransferase
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Parkin N T
Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
Cohen E A
Darveau A
Rosen C
Haseltine W
Sonenberg N
References (37)
37 references, click to expand
  1. Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS.
    Science. 1984 May 4;224(4648):497-500 PMID: 6200935
  2. Intragenic cis-acting art gene-responsive sequences of the human immunodeficiency virus.
    Proc Natl Acad Sci U S A. 1988 Apr;85(7):2071-5 PMID: 2832844
  3. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter.
    Nucleic Acids Res. 1984 Sep 25;12(18):7035-56 PMID: 6091052
  4. Trans-acting transcriptional regulation of human T-cell leukemia virus type III long terminal repeat.
    Science. 1985 Jan 11;227(4683):171-3 PMID: 2981427
  5. Insertion mutagenesis to increase secondary structure within the 5' noncoding region of a eukaryotic mRNA reduces translational efficiency.
    Cell. 1985 Mar;40(3):515-26 PMID: 2982496
  6. Cap accessibility correlates with the initiation efficiency of alfalfa mosaic virus RNAs.
    Eur J Biochem. 1985 Mar 15;147(3):549-52 PMID: 2983983
  7. The location of cis-acting regulatory sequences in the human T cell lymphotropic virus type III (HTLV-III/LAV) long terminal repeat.
    Cell. 1985 Jul;41(3):813-23 PMID: 2988790
  8. Trans-activator gene of human T-lymphotropic virus type III (HTLV-III).
    Science. 1985 Jul 5;229(4708):69-73 PMID: 2990040
  9. Location of the trans-activating region on the genome of human T-cell lymphotropic virus type III.
    Science. 1985 Jul 5;229(4708):74-7 PMID: 2990041
  10. The epidemiology of AIDS: current status and future prospects.
    Science. 1985 Sep 27;229(4720):1352-7 PMID: 2994217
  11. Post-transcriptional regulation accounts for the trans-activation of the human T-lymphotropic virus type III.
    Nature. 1986 Feb 13-19;319(6054):555-9 PMID: 3003584
  12. Long-term cultures of HTLV-III--infected T cells: a model of cytopathology of T-cell depletion in AIDS.
    Science. 1986 Feb 21;231(4740):850-3 PMID: 2418502
  13. A second post-transcriptional trans-activator gene required for HTLV-III replication.
    Nature. 1986 May 22-28;321(6068):412-7 PMID: 3012355
  14. Photochemical cross-linking of cap binding proteins to eucaryotic mRNAs: effect of mRNA 5' secondary structure.
    Mol Cell Biol. 1985 Nov;5(11):3222-30 PMID: 3837842
  15. 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
  16. Trans-activation of human immunodeficiency virus occurs via a bimodal mechanism.
    Cell. 1986 Sep 26;46(7):973-82 PMID: 3530501
  17. Demonstration of virus-specific transcriptional activator(s) in cells infected with HTLV-III by an in vitro cell-free system.
    Cell. 1986 Oct 10;47(1):29-35 PMID: 3019564
  18. Expression and characterization of the trans-activator of HTLV-III/LAV virus.
    Science. 1986 Nov 21;234(4779):988-92 PMID: 3490693
  19. Elevated levels of mRNA can account for the trans-activation of human immunodeficiency virus.
    Proc Natl Acad Sci U S A. 1986 Dec;83(24):9734-8 PMID: 3025848
  20. Regulation of mRNA accumulation by a human immunodeficiency virus trans-activator protein.
    Cell. 1987 Feb 27;48(4):691-701 PMID: 3643816
  21. Expression of the art/trs protein of HIV and study of its role in viral envelope synthesis.
    Science. 1987 May 15;236(4803):837-40 PMID: 3033827
  22. Transcription directed by the HIV long terminal repeat in vitro.
    AIDS Res Hum Retroviruses. 1987 Spring;3(1):41-55 PMID: 3040054
  23. Anti-termination of transcription within the long terminal repeat of HIV-1 by tat gene product.
    Nature. 1987 Dec 3-9;330(6147):489-93 PMID: 2825027
  24. Improved estimation of secondary structure in ribonucleic acids.
    Nat New Biol. 1973 Nov 14;246(150):40-1 PMID: 4519026
  25. An efficient mRNA-dependent translation system from reticulocyte lysates.
    Eur J Biochem. 1976 AUG 1;67(1):247-56 PMID: 823012
  26. DNA sequencing with chain-terminating inhibitors.
    Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 PMID: 271968
  27. Inhibition of translation by poliovirus: inactivation of a specific initiation factor.
    Proc Natl Acad Sci U S A. 1978 Jun;75(6):2732-6 PMID: 208073
  28. Transcriptional regulation of the yeast cytochrome c gene.
    Proc Natl Acad Sci U S A. 1979 Aug;76(8):3627-31 PMID: 226972
  29. Interference of nonsense mutations with eukaryotic messenger RNA stability.
    Proc Natl Acad Sci U S A. 1979 Oct;76(10):5134-7 PMID: 388431
  30. Sequencing end-labeled DNA with base-specific chemical cleavages.
    Methods Enzymol. 1980;65(1):499-560 PMID: 6246368
  31. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells.
    Mol Cell Biol. 1982 Sep;2(9):1044-51 PMID: 6960240
  32. Oligonucleotide-directed mutagenesis using M13-derived vectors: an efficient and general procedure for the production of point mutations in any fragment of DNA.
    Nucleic Acids Res. 1982 Oct 25;10(20):6487-500 PMID: 6757864
  33. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS).
    Science. 1983 May 20;220(4599):868-71 PMID: 6189183
  34. The involvement of mRNA secondary structure in protein synthesis.
    Biochem Cell Biol. 1987 Jun;65(6):576-81 PMID: 3322328
  35. Site-directed mutagenesis of two trans-regulatory genes (tat-III,trs) of HIV-1.
    Science. 1988 Feb 19;239(4842):910-3 PMID: 3277284
  36. Double stranded DNA sequencing as a choice for DNA sequencing.
    Nucleic Acids Res. 1988 Feb 11;16(3):1220 PMID: 3344219
  37. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS.
    Science. 1984 May 4;224(4648):500-3 PMID: 6200936
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1988-09-00
Pages
2831-7
Language
English
Region
England
NLM ID
8208664
PMCID
PMC457075
Subset
IM
Grants
NCI NIH HHS · CA42098 · United States
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