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An internal polypyrimidine-tract-binding protein-binding site in the hepatitis C virus RNA attenuates translation, which is relieved by the 3'-untranslated sequence.
Virology. 1999 Feb 15; 254(2):288-96.V

Abstract

Hepatitis C virus (HCV) RNA binds to several cellular proteins, which may regulate translation or replication of viral RNA. One of these is polypyrimidine tract-binding protein (PTB), which binds to the 5'-untranslated region (UTR) and the 3'-end 98 nucleotides (nt) (X region) of HCV RNA. Both of these PTB-binding sites regulate HCV translation. In this study, we further investigated the nature of PTB binding on HCV RNA. UV cross-linking studies using HeLa cell extracts and a recombinant PTB showed that the PTB-5'-UTR binding was much weaker than the PTB-3'-UTR binding. Unexpectedly, we found an even stronger PTB-binding site in the core-protein-coding region of HCV RNA. The binding domain was mapped to the 3'-end of this region, which contains a pyrimidine-rich sequence highly conserved among HCV isolates. Using a set of synthetic HCV RNAs with or without this sequence in in vitro translation studies, we showed that the PTB-binding sequence in the core-coding region strongly inhibited translation of HCV RNA. This inhibition was relieved by the presence of the X region at the 3'-end. Furthermore, the previously reported translational enhancement by the HCV 3'-UTR was more pronounced when this PTB-binding site was present in the RNA. These results suggest that PTB binding to an internal site of HCV RNA provides another mechanism for regulation of HCV translation.

Authors+Show Affiliations

Department of Molecular Microbiology and Immunology, University of Southern California School of Medicine, Los Angeles, California, 90033-1054, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9986795

Citation

Ito, T, and M M. Lai. "An Internal Polypyrimidine-tract-binding Protein-binding Site in the Hepatitis C Virus RNA Attenuates Translation, Which Is Relieved By the 3'-untranslated Sequence." Virology, vol. 254, no. 2, 1999, pp. 288-96.
Ito T, Lai MM. An internal polypyrimidine-tract-binding protein-binding site in the hepatitis C virus RNA attenuates translation, which is relieved by the 3'-untranslated sequence. Virology. 1999;254(2):288-96.
Ito, T., & Lai, M. M. (1999). An internal polypyrimidine-tract-binding protein-binding site in the hepatitis C virus RNA attenuates translation, which is relieved by the 3'-untranslated sequence. Virology, 254(2), 288-96.
Ito T, Lai MM. An Internal Polypyrimidine-tract-binding Protein-binding Site in the Hepatitis C Virus RNA Attenuates Translation, Which Is Relieved By the 3'-untranslated Sequence. Virology. 1999 Feb 15;254(2):288-96. PubMed PMID: 9986795.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - An internal polypyrimidine-tract-binding protein-binding site in the hepatitis C virus RNA attenuates translation, which is relieved by the 3'-untranslated sequence. AU - Ito,T, AU - Lai,M M, PY - 1999/2/13/pubmed PY - 1999/2/13/medline PY - 1999/2/13/entrez SP - 288 EP - 96 JF - Virology JO - Virology VL - 254 IS - 2 N2 - Hepatitis C virus (HCV) RNA binds to several cellular proteins, which may regulate translation or replication of viral RNA. One of these is polypyrimidine tract-binding protein (PTB), which binds to the 5'-untranslated region (UTR) and the 3'-end 98 nucleotides (nt) (X region) of HCV RNA. Both of these PTB-binding sites regulate HCV translation. In this study, we further investigated the nature of PTB binding on HCV RNA. UV cross-linking studies using HeLa cell extracts and a recombinant PTB showed that the PTB-5'-UTR binding was much weaker than the PTB-3'-UTR binding. Unexpectedly, we found an even stronger PTB-binding site in the core-protein-coding region of HCV RNA. The binding domain was mapped to the 3'-end of this region, which contains a pyrimidine-rich sequence highly conserved among HCV isolates. Using a set of synthetic HCV RNAs with or without this sequence in in vitro translation studies, we showed that the PTB-binding sequence in the core-coding region strongly inhibited translation of HCV RNA. This inhibition was relieved by the presence of the X region at the 3'-end. Furthermore, the previously reported translational enhancement by the HCV 3'-UTR was more pronounced when this PTB-binding site was present in the RNA. These results suggest that PTB binding to an internal site of HCV RNA provides another mechanism for regulation of HCV translation. SN - 0042-6822 UR - https://www.unboundmedicine.com/medline/citation/9986795/An_internal_polypyrimidine_tract_binding_protein_binding_site_in_the_hepatitis_C_virus_RNA_attenuates_translation_which_is_relieved_by_the_3'_untranslated_sequence_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0042-6822(98)99541-1 DB - PRIME DP - Unbound Medicine ER -