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Journal of Virology, November 1998, p. 8789-8796, Vol. 72, No. 11
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

The 3'-Untranslated Region of Hepatitis C Virus RNA Enhances Translation from an Internal Ribosomal Entry Site

Takayoshi Ito,1 Stanley M. Tahara,2 and Michael M. C. Lai1,2,*

Howard Hughes Medical Institute1 and Department of Molecular Microbiology and Immunology,2 University of Southern California School of Medicine, Los Angeles, California 90033-1054

Received 26 May 1998/Accepted 12 August 1998

Translation of most eukaryotic mRNAs and many viral RNAs is enhanced by their poly(A) tails. Hepatitis C virus (HCV) contains a positive-stranded RNA genome which does not have a poly(A) tail but has a stretch of 98 nucleotides (X region) at the 3'-untranslated region (UTR), which assumes a highly conserved stem-loop structure. This X region binds a polypyrimidine tract-binding protein (PTB), which also binds to the internal ribosome entry site (IRES) in HCV 5'-UTR. These RNA-protein interactions may regulate its translation. We generated a set of HCV RNAs differing only in their 3'-UTRs and compared their translation efficiencies. HCV RNA containing the X region was translated three- to fivefold more than the corresponding RNAs without this region. Mutations that abolished PTB binding in the X region reduced, but did not completely abolish, enhancement in translation. The X region also enhanced translation from another unrelated IRES (from encephalomyocarditis virus RNA), but did not affect the 5'-end-dependent translation of globin mRNA in either monocistronic or bicistronic RNAs. It did not appear to affect RNA stability. The free X region added in trans, however, did not enhance translation, indicating that the translational enhancement by the X region occurs only in cis. These results demonstrate that the highly conserved 3' end of HCV RNA provides a novel mechanism for enhancement of HCV translation and may offer a target for antiviral agents.

* Corresponding author. Mailing address: Department of Molecular Microbiology and Immunology, University of Southern California School of Medicine, 2011 Zonal Ave., HMR-503, Los Angeles, CA 90033-1054. Phone: (323) 442-1748. Fax: (323) 342-9555. E-mail: michlai{at}hsc.usc.edu.

Journal of Virology, November 1998, p. 8789-8796, Vol. 72, No. 11
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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