Triple decoding of hepatitis C virus RNA by programmed translational frameshifting.
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.
Choi
Jinah
J
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
Xu
Zhenming
Z
Ou
Jing-hsiung
JH
D000595:Amino Acid Sequence; D001483:Base Sequence; D015153:Blotting, Western; D003062:Codon; D004305:Dose-Response Relationship, Drug; D016368:Frameshift Mutation; D017930:Genes, Reporter; D016174:Hepacivirus / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D016366:Open Reading Frames; D010458:Peptidyl Transferases / Q000037:antagonists & inhibitors; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D014176:Protein Biosynthesis; D011691:Puromycin / Q000494:pharmacology; D012367:RNA, Viral / Q000235:genetics*; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D003062:Codon; D012367:RNA, Viral; D011691:Puromycin; D010458:Peptidyl Transferases