SrasV1, Main, Exploration, bibRecord, 002024

The many paths to frameshifting: kinetic modelling and analysis of the effects of different elongation steps on programmed -1 ribosomal frameshifting.

Identifieur interne : 002024 ( Main/Exploration ); précédent : 002023; suivant : 002025

The many paths to frameshifting: kinetic modelling and analysis of the effects of different elongation steps on programmed -1 ribosomal frameshifting.

Auteurs : Pei-Yu Liao [États-Unis] ; Yong Seok Choi ; Jonathan D. Dinman ; Kelvin H. Lee

Source :

Nucleic acids research [ 1362-4962 ] ; 2011.

RBID : pubmed:20823091

Descripteurs français

English descriptors

KwdEn :
- Frameshifting, Ribosomal, HIV-1 (genetics), Human T-lymphotropic virus 1 (genetics), Kinetics, Mass Spectrometry, Models, Genetic, Peptide Chain Elongation, Translational, RNA, Transfer (metabolism), Ribosomes (metabolism).
MESH :
- chemical , metabolism : RNA, Transfer.
- genetics : HIV-1, Human T-lymphotropic virus 1.
- metabolism : Ribosomes.
- Frameshifting, Ribosomal, Kinetics, Mass Spectrometry, Models, Genetic, Peptide Chain Elongation, Translational.

Abstract

Several important viruses including the human immunodeficiency virus type 1 (HIV-1) and the SARS-associated Coronavirus (SARS-CoV) employ programmed -1 ribosomal frameshifting (PRF) for their protein expression. Here, a kinetic framework is developed to describe -1 PRF. The model reveals three kinetic pathways to -1 PRF that yield two possible frameshift products: those incorporating zero frame encoded A-site tRNAs in the recoding site, and products incorporating -1 frame encoded A-site tRNAs. Using known kinetic rate constants, the individual contributions of different steps of the translation elongation cycle to -1 PRF and the ratio between two types of frameshift products were evaluated. A dual fluorescence reporter was employed in Escherichia coli to empirically test the model. Additionally, the study applied a novel mass spectrometry approach to quantify the ratios of the two frameshift products. A more detailed understanding of the mechanisms underlying -1 PRF may provide insight into developing antiviral therapeutics.

DOI: 10.1093/nar/gkq761
PubMed: 20823091

Affiliations:

Le document en format XML

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<front><div type="abstract" xml:lang="en">Several important viruses including the human immunodeficiency virus type 1 (HIV-1) and the SARS-associated Coronavirus (SARS-CoV) employ programmed -1 ribosomal frameshifting (PRF) for their protein expression. Here, a kinetic framework is developed to describe -1 PRF. The model reveals three kinetic pathways to -1 PRF that yield two possible frameshift products: those incorporating zero frame encoded A-site tRNAs in the recoding site, and products incorporating -1 frame encoded A-site tRNAs. Using known kinetic rate constants, the individual contributions of different steps of the translation elongation cycle to -1 PRF and the ratio between two types of frameshift products were evaluated. A dual fluorescence reporter was employed in Escherichia coli to empirically test the model. Additionally, the study applied a novel mass spectrometry approach to quantify the ratios of the two frameshift products. A more detailed understanding of the mechanisms underlying -1 PRF may provide insight into developing antiviral therapeutics.</div>
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The many paths to frameshifting: kinetic modelling and analysis of the effects of different elongation steps on programmed -1 ribosomal frameshifting.

The many paths to frameshifting: kinetic modelling and analysis of the effects of different elongation steps on programmed -1 ribosomal frameshifting.

Source :

Descripteurs français

English descriptors

Abstract

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