Characterization of ribosomal frameshifting in HIV-1 gag-pol expression

Tyler Jacks, Michael D. Power, Frank R. Masiarz, Paul A Luciw, Philip J. Barr, Harold E. Varmus

Research output: Contribution to journalArticle

601 Citations (Scopus)

Abstract

Based on precedents from other retro viruses1, the precursor of the human immunodeficiency virus (HIV-1) reverse transcriptase is predicted to be a polyprotein with a relative molecular mass (Mr) of 160,000 (160K) encoded by both the viral pol gene and the upstream gag gene. These two genes lie in different translational reading frames, with the 3′ end of gag overlapping the 5′ end of pol by 205 or 241 nucleotides2-4. Thus, production of the gag-pol fusion protein would require either messenger RNA processing or translational frameshifting. The latter mechanism has been shown in the synthesis of the gag-pol proteins of two other retroviruses, Rous sarcoma virus (RSV)5 and mouse mammary tumour virus (MMTV) 6-7. Here we report that translation of HIV-1 RNA synthesized in vitro by SP6 RNA polymerase yields significant amounts of a gag-pol fusion protein, indicating that efficient ribosomal frameshifting also occurs within the HIV-1 gag-pol overlap region. Site-directed mutagenesis and amino-acid sequencing localized the site of frameshifting to a UUA leucine codon near the 5′ end of the overlap.

Original languageEnglish (US)
Pages (from-to)280-283
Number of pages4
JournalNature
Volume331
Issue number6153
StatePublished - 1988

Fingerprint

gag-pol Fusion Proteins
Ribosomal Frameshifting
HIV-1
pol Genes
gag Genes
Mouse mammary tumor virus
Polyproteins
Rous sarcoma virus
Reading Frames
Viral Genes
Protein Sequence Analysis
Retroviridae
Site-Directed Mutagenesis
Codon
Leucine
RNA
Messenger RNA
Genes
Human immunodeficiency virus 1 reverse transcriptase

ASJC Scopus subject areas

  • General

Cite this

Jacks, T., Power, M. D., Masiarz, F. R., Luciw, P. A., Barr, P. J., & Varmus, H. E. (1988). Characterization of ribosomal frameshifting in HIV-1 gag-pol expression. Nature, 331(6153), 280-283.

Characterization of ribosomal frameshifting in HIV-1 gag-pol expression. / Jacks, Tyler; Power, Michael D.; Masiarz, Frank R.; Luciw, Paul A; Barr, Philip J.; Varmus, Harold E.

In: Nature, Vol. 331, No. 6153, 1988, p. 280-283.

Research output: Contribution to journalArticle

Jacks, T, Power, MD, Masiarz, FR, Luciw, PA, Barr, PJ & Varmus, HE 1988, 'Characterization of ribosomal frameshifting in HIV-1 gag-pol expression', Nature, vol. 331, no. 6153, pp. 280-283.
Jacks T, Power MD, Masiarz FR, Luciw PA, Barr PJ, Varmus HE. Characterization of ribosomal frameshifting in HIV-1 gag-pol expression. Nature. 1988;331(6153):280-283.
Jacks, Tyler ; Power, Michael D. ; Masiarz, Frank R. ; Luciw, Paul A ; Barr, Philip J. ; Varmus, Harold E. / Characterization of ribosomal frameshifting in HIV-1 gag-pol expression. In: Nature. 1988 ; Vol. 331, No. 6153. pp. 280-283.
@article{ee74af1aeebe4a8999ea64c6273a6812,
title = "Characterization of ribosomal frameshifting in HIV-1 gag-pol expression",
abstract = "Based on precedents from other retro viruses1, the precursor of the human immunodeficiency virus (HIV-1) reverse transcriptase is predicted to be a polyprotein with a relative molecular mass (Mr) of 160,000 (160K) encoded by both the viral pol gene and the upstream gag gene. These two genes lie in different translational reading frames, with the 3′ end of gag overlapping the 5′ end of pol by 205 or 241 nucleotides2-4. Thus, production of the gag-pol fusion protein would require either messenger RNA processing or translational frameshifting. The latter mechanism has been shown in the synthesis of the gag-pol proteins of two other retroviruses, Rous sarcoma virus (RSV)5 and mouse mammary tumour virus (MMTV) 6-7. Here we report that translation of HIV-1 RNA synthesized in vitro by SP6 RNA polymerase yields significant amounts of a gag-pol fusion protein, indicating that efficient ribosomal frameshifting also occurs within the HIV-1 gag-pol overlap region. Site-directed mutagenesis and amino-acid sequencing localized the site of frameshifting to a UUA leucine codon near the 5′ end of the overlap.",
author = "Tyler Jacks and Power, {Michael D.} and Masiarz, {Frank R.} and Luciw, {Paul A} and Barr, {Philip J.} and Varmus, {Harold E.}",
year = "1988",
language = "English (US)",
volume = "331",
pages = "280--283",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "6153",

}

TY - JOUR

T1 - Characterization of ribosomal frameshifting in HIV-1 gag-pol expression

AU - Jacks, Tyler

AU - Power, Michael D.

AU - Masiarz, Frank R.

AU - Luciw, Paul A

AU - Barr, Philip J.

AU - Varmus, Harold E.

PY - 1988

Y1 - 1988

N2 - Based on precedents from other retro viruses1, the precursor of the human immunodeficiency virus (HIV-1) reverse transcriptase is predicted to be a polyprotein with a relative molecular mass (Mr) of 160,000 (160K) encoded by both the viral pol gene and the upstream gag gene. These two genes lie in different translational reading frames, with the 3′ end of gag overlapping the 5′ end of pol by 205 or 241 nucleotides2-4. Thus, production of the gag-pol fusion protein would require either messenger RNA processing or translational frameshifting. The latter mechanism has been shown in the synthesis of the gag-pol proteins of two other retroviruses, Rous sarcoma virus (RSV)5 and mouse mammary tumour virus (MMTV) 6-7. Here we report that translation of HIV-1 RNA synthesized in vitro by SP6 RNA polymerase yields significant amounts of a gag-pol fusion protein, indicating that efficient ribosomal frameshifting also occurs within the HIV-1 gag-pol overlap region. Site-directed mutagenesis and amino-acid sequencing localized the site of frameshifting to a UUA leucine codon near the 5′ end of the overlap.

AB - Based on precedents from other retro viruses1, the precursor of the human immunodeficiency virus (HIV-1) reverse transcriptase is predicted to be a polyprotein with a relative molecular mass (Mr) of 160,000 (160K) encoded by both the viral pol gene and the upstream gag gene. These two genes lie in different translational reading frames, with the 3′ end of gag overlapping the 5′ end of pol by 205 or 241 nucleotides2-4. Thus, production of the gag-pol fusion protein would require either messenger RNA processing or translational frameshifting. The latter mechanism has been shown in the synthesis of the gag-pol proteins of two other retroviruses, Rous sarcoma virus (RSV)5 and mouse mammary tumour virus (MMTV) 6-7. Here we report that translation of HIV-1 RNA synthesized in vitro by SP6 RNA polymerase yields significant amounts of a gag-pol fusion protein, indicating that efficient ribosomal frameshifting also occurs within the HIV-1 gag-pol overlap region. Site-directed mutagenesis and amino-acid sequencing localized the site of frameshifting to a UUA leucine codon near the 5′ end of the overlap.

UR - http://www.scopus.com/inward/record.url?scp=0023870815&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023870815&partnerID=8YFLogxK

M3 - Article

C2 - 2447506

AN - SCOPUS:0023870815

VL - 331

SP - 280

EP - 283

JO - Nature

JF - Nature

SN - 0028-0836

IS - 6153

ER -