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Molecular and Cellular Biology, March 2003, p. 1489-1497, Vol. 23, No. 5
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.5.1489-1497.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Triple Decoding of Hepatitis C Virus RNA by Programmed Translational Frameshifting

Jinah Choi, Zhenming Xu, and Jing-hsiung Ou*

Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033,

Received 12 June 2002/ Returned for modification 21 August 2002/ Accepted 27 November 2002

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.

* Corresponding author. Mailing address: Department of Molecular Microbiology & Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Ave., Los Angeles, CA 90033. Phone: (323) 442-1720. Fax: (323) 442-1721. E-mail: jamesou{at}hsc.usc.edu.

Molecular and Cellular Biology, March 2003, p. 1489-1497, Vol. 23, No. 5
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.5.1489-1497.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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