Triple Decoding of Hepatitis C Virus RNA by Programmed Translational Frameshifting

Abstract

Ribosomes can be programmed to shift from one reading frame to another during translation. Hepatitis C virus (HCV) uses such a mechanism to produce F protein from the −2/+1 reading frame. We now report that the HCV frameshift signal can mediate the synthesis of the core protein of the zero frame, the F protein of the −2/+1 frame, and a 1.5-kDa protein of the −1/+2 frame. This triple decoding function does not require sequences flanking the frameshift signal and is apparently independent of membranes and the synthesis of the HCV polyprotein. Two consensus −1 frameshift sequences in the HCV type 1 frameshift signal facilitate ribosomal frameshifts into both overlapping reading frames. A sequence which is located immediately downstream of the frameshift signal and has the potential to form a double stem-loop structure can significantly enhance translational frameshifting in the presence of the peptidyl-transferase inhibitor puromycin. Based on these results, a model is proposed to explain the triple decoding activities of the HCV ribosomal frameshift signal.

ACKNOWLEDGMENTS

We thank Ben Yen for critical reading of the manuscript and members of J. Ou's laboratory for helpful discussions throughout this entire project.

This work was supported by postdoctoral fellowship PF-01-037-01-MBC to J.C. from the American Cancer Society and a grant from the National Institutes of Health.