Interaction of Polypyrimidine Tract-binding Protein with the 5' Noncoding Region of the Hepatitis C Virus RNA Genome and Its Functional Requirement in Internal Initiation of Translation

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 1995 Oct 1

PMID 7666538

Citations 88

Authors

N Ali

A Siddiqui

Affiliations

Soon will be listed here.

Abstract

Initiation of translation of the human hepatitis C virus (HCV) RNA genome occurs by internal ribosome entry into the 5' noncoding region (5'NCR) in a cap-independent manner. The internal ribosome entry site of the HCV 5'NCR has been previously defined to encompass almost the entire 5'NCR. Here we report the interaction of polypyrimidine tract-binding protein (PTB) at three distinct regions within the 5'NCR by UV cross-linking assays. All three regions contain a consensus polypyrimidine tract motif. The evidence for the interaction of recombinant PTB at multiple sites within the 5'NCR is based on the use of 5'NCR mutants as competitors and by direct UV cross-linking of the mutant RNAs. Furthermore, the PTB isomers from HeLa nuclear extracts interact with the HCV 5'NCR, as shown by immunoprecipitation of a UV cross-linked complex with anti-PTB serum. Immunodepletion of PTB from translation lysates suggested the functional requirement for PTB during translation initiation of the HCV RNA. Addition of purified PTB to immunodepleted lysates did not restore translation mediated by the HCV 5'NCR, indicating the requirement of PTB-associated factors that were removed during immunodepletion.

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References

Tsukuma H, Hiyama T, Tanaka S, Nakao M, Yabuuchi T, Kitamura T . Risk factors for hepatocellular carcinoma among patients with chronic liver disease. N Engl J Med. 1993; 328(25):1797-801. DOI: 10.1056/NEJM199306243282501. View

Miller R, Purcell R . Hepatitis C virus shares amino acid sequence similarity with pestiviruses and flaviviruses as well as members of two plant virus supergroups. Proc Natl Acad Sci U S A. 1990; 87(6):2057-61. PMC: 53625. DOI: 10.1073/pnas.87.6.2057. View

Witherell G, Gil A, Wimmer E . Interaction of polypyrimidine tract binding protein with the encephalomyocarditis virus mRNA internal ribosomal entry site. Biochemistry. 1993; 32(32):8268-75. DOI: 10.1021/bi00083a030. View

Hellen C, Witherell G, Schmid M, Shin S, Pestova T, Gil A . A cytoplasmic 57-kDa protein that is required for translation of picornavirus RNA by internal ribosomal entry is identical to the nuclear pyrimidine tract-binding protein. Proc Natl Acad Sci U S A. 1993; 90(16):7642-6. PMC: 47198. DOI: 10.1073/pnas.90.16.7642. View

Borman A, Howell M, Patton J, Jackson R . The involvement of a spliceosome component in internal initiation of human rhinovirus RNA translation. J Gen Virol. 1993; 74 ( Pt 9):1775-88. DOI: 10.1099/0022-1317-74-9-1775. View

Chang K, Brown E, Lemon S . Cell type-specific proteins which interact with the 5' nontranslated region of hepatitis A virus RNA. J Virol. 1993; 67(11):6716-25. PMC: 238111. DOI: 10.1128/JVI.67.11.6716-6725.1993. View

Hellen C, Pestova T, Litterst M, Wimmer E . The cellular polypeptide p57 (pyrimidine tract-binding protein) binds to multiple sites in the poliovirus 5' nontranslated region. J Virol. 1994; 68(2):941-50. PMC: 236532. DOI: 10.1128/JVI.68.2.941-950.1994. View

Svitkin Y, Meerovitch K, Lee H, Dholakia J, Kenan D, Agol V . Internal translation initiation on poliovirus RNA: further characterization of La function in poliovirus translation in vitro. J Virol. 1994; 68(3):1544-50. PMC: 236611. DOI: 10.1128/JVI.68.3.1544-1550.1994. View

Witherell G, Wimmer E . Encephalomyocarditis virus internal ribosomal entry site RNA-protein interactions. J Virol. 1994; 68(5):3183-92. PMC: 236809. DOI: 10.1128/JVI.68.5.3183-3192.1994. View

10.

Wakita T, Wands J . Specific inhibition of hepatitis C virus expression by antisense oligodeoxynucleotides. In vitro model for selection of target sequence. J Biol Chem. 1994; 269(19):14205-10. View

11.

EHRENFELD E, Gebhard J . Interaction of cellular proteins with the poliovirus 5' noncoding region. Arch Virol Suppl. 1994; 9:269-77. DOI: 10.1007/978-3-7091-9326-6_27. View

12.

Schmid M, Wimmer E . IRES-controlled protein synthesis and genome replication of poliovirus. Arch Virol Suppl. 1994; 9:279-89. DOI: 10.1007/978-3-7091-9326-6_28. View

13.

Sonenberg N . Poliovirus translation. Curr Top Microbiol Immunol. 1990; 161:23-47. DOI: 10.1007/978-3-642-75602-3_2. View

14.

Jang S, Wimmer E . Cap-independent translation of encephalomyocarditis virus RNA: structural elements of the internal ribosomal entry site and involvement of a cellular 57-kD RNA-binding protein. Genes Dev. 1990; 4(9):1560-72. DOI: 10.1101/gad.4.9.1560. View

15.

Kato N, Hijikata M, Ootsuyama Y, Nakagawa M, Ohkoshi S, Sugimura T . Molecular cloning of the human hepatitis C virus genome from Japanese patients with non-A, non-B hepatitis. Proc Natl Acad Sci U S A. 1990; 87(24):9524-8. PMC: 55204. DOI: 10.1073/pnas.87.24.9524. View

16.

Takamizawa A, Mori C, FUKE I, Manabe S, Murakami S, Fujita J . Structure and organization of the hepatitis C virus genome isolated from human carriers. J Virol. 1991; 65(3):1105-13. PMC: 239876. DOI: 10.1128/JVI.65.3.1105-1113.1991. View

17.

Han J, Shyamala V, Richman K, BRAUER M, Irvine B, Urdea M . Characterization of the terminal regions of hepatitis C viral RNA: identification of conserved sequences in the 5' untranslated region and poly(A) tails at the 3' end. Proc Natl Acad Sci U S A. 1991; 88(5):1711-5. PMC: 51094. DOI: 10.1073/pnas.88.5.1711. View

18.

Choo Q, Richman K, Han J, Berger K, Lee C, Dong C . Genetic organization and diversity of the hepatitis C virus. Proc Natl Acad Sci U S A. 1991; 88(6):2451-5. PMC: 51250. DOI: 10.1073/pnas.88.6.2451. View

19.

Jackson R, Howell M, Kaminski A . The novel mechanism of initiation of picornavirus RNA translation. Trends Biochem Sci. 1990; 15(12):477-83. DOI: 10.1016/0968-0004(90)90302-r. View

20.

Gil A, Sharp P, Jamison S, Garcia-Blanco M . Characterization of cDNAs encoding the polypyrimidine tract-binding protein. Genes Dev. 1991; 5(7):1224-36. DOI: 10.1101/gad.5.7.1224. View