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Triple decoding of hepatitis C virus RNA by programmed translational frameshifting
Jinah Choi1, Zhenming Xu, Jing-hsiung Ou
1Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
Molecular and Cellular Biology
|February 18, 2003
Summary
Hepatitis C virus (HCV) translation exhibits triple decoding, producing three proteins from one RNA sequence. This frameshift mechanism is independent of host cell membranes and polyprotein synthesis.
Area of Science:
- Molecular Biology
- Virology
- Biochemistry
Background:
- Ribosomes can alter their reading frame during protein synthesis.
- Hepatitis C virus (HCV) utilizes programmed ribosomal frameshifting to produce its F protein.
Purpose of the Study:
- To investigate the full translational decoding capacity of the HCV frameshift signal.
- To elucidate the mechanisms underlying HCV's multi-protein synthesis from a single RNA segment.
Main Methods:
- Analysis of protein synthesis from the HCV frameshift signal in vitro.
- Identification of translated products from zero, -2/+1, and -1/+2 reading frames.
- Assessment of frameshifting efficiency with and without flanking sequences and puromycin.
Main Results:
- The HCV frameshift signal directs the synthesis of three distinct proteins: core (0 frame), F protein (-2/+1 frame), and a 1.5-kDa protein (-1/+2 frame).
- This triple decoding function is independent of flanking sequences, membranes, and polyprotein synthesis.
- Two consensus -1 frameshift sequences and a downstream double stem-loop structure enhance ribosomal frameshifting.
Conclusions:
- The HCV frameshift signal possesses a remarkable triple decoding capability, expanding the viral proteome from a single reading frame.
- A model is proposed to explain the molecular basis of this complex translational control.
- Understanding this mechanism offers insights into viral gene expression strategies.