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The 39-untranslated region of hepatitis C virus RNA enhances translation from an internal ribosomal entry site (1998)

by T Ito, Tahara SM, Lai MM
Venue:J Virol
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A recombinant hepatitis C virus RNA-dependent RNA polymerase capable of copying the full-length viral RNA

by Jong-won Oh, Takayoshi Ito, Michael M. C. Lai, Updated Information, Jong-won Oh, Takayoshi Ito, Michael M. C. Lai - J , 1999
"... These include: This article cites 48 articles, 32 of which can be accessed free at: ..."
Abstract - Cited by 64 (2 self) - Add to MetaCart
These include: This article cites 48 articles, 32 of which can be accessed free at:
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...) (16, 40). The PTBbinding sites were mapped to stem-loop structures 2 and 3 of the X region (16). The X region has been shown to enhance HCV translation, possibly through interaction with the 5� end =-=(17)-=-. Conceivably, the 3�-end sequence may also be important for HCV RNA replication, because it likely includes the cisacting signals for RNA replication. The HCV NS5B is at the C terminus of the HCV pol...

De novo initiation of RNA synthesis by the RNAdependent RNA polymerase (NS5B) of hepatitis C virus

by Guangxiang Luo, Robert K. Hamatake, Danielle M. Mathis, Jason Racela, Karen L. Rigat, Julie Lemm, Richard J, Guangxiang Luo, Robert K. Hamatake, Danielle M. Mathis, Jason Racela, Karen L. Rigat, Julie Lemm, Richard, J. Colonno - J , 2000
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...cent studies have revealed that two cellular proteins, p58 (PTB) and p35, specifically interact with the 3� UTR (26, 39, 60) and may be involved in regulating the translation of the viral polyprotein =-=(27)-=- or viral replication. Unlike what is found for other RNA viruses, to which reverse genetics is applicable (1, 47, 64), functions of the cis signal sequences and viral proteins of HCV in the context o...

Translational control of viral gene expression in eukaryotes

by Michael Gale, Seng-lai Tan, Michael G. Katze, Michael Gale , 2000
"... This article cites 464 articles, 249 of which can be accessed ..."
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...the HCV IRES. In these studies, Ito and Lai found that the core region pyrimidine-rich sequence had a suppressive effect on IRES-mediated translation, most likely induced through interaction with PTB =-=(217, 218)-=-. This translational suppression was relieved by an interaction of PTB with the highly conserved 98 nt of the HCV 3� UTR. These results are consistent with the idea that sequences outside the HCV IRES...

2002. Genetic analysis of sequences in the 3 nontranslated region of hepatitis C virus that are important for RNA replication

by Peter Friebe, Ralf Bartenschlager - J
"... The genome of the hepatitis C virus (HCV) is a plus-strand RNA molecule that carries a single long open reading frame. It is flanked at either end by highly conserved nontranslated regions (NTRs) that mediate crucial steps in the viral life cycle. The 3 NTR of HCV has a tripartite structure compose ..."
Abstract - Cited by 48 (8 self) - Add to MetaCart
The genome of the hepatitis C virus (HCV) is a plus-strand RNA molecule that carries a single long open reading frame. It is flanked at either end by highly conserved nontranslated regions (NTRs) that mediate crucial steps in the viral life cycle. The 3 NTR of HCV has a tripartite structure composed of an about 40-nucleotide variable region, a poly(U/UC) tract that has a heterogeneous length, and a highly conserved 98-nucleotide 3-terminal sequence designated the X tail or 3X. Conflicting data as to the role the sequences in the 3 NTR play in RNA replication have been reported. By using the HCV replicon system, which is based on the self-replication of subgenomic HCV RNAs in human hepatoma cell line Huh-7, we mapped in this study the sequences in the 3 NTR required for RNA replication. We found that a mutant with a complete deletion of the variable region is viable but that replication is reduced significantly. Only replicons in which the poly(U/UC) tract was replaced by a homouridine stretch of at least 26 nucleotides were able to replicate, whereas RNAs with homopolymeric guanine, adenine, or cytosine sequences were inactive. Deletions of indi-vidual or all stem-loop structures in 3X were not tolerated, demonstrating that this region is most crucial for efficient RNA replication. Finally, we found that none of these deletions or substitutions within the 3 NTR affected RNA stability or translation, demonstrating that the primary effect of the mutations was on RNA replication. These data represent the first detailed mapping of sequences in the 3 NTR assumed to act as a
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... Recent studies suggest that, in addition to playing a major role in RNA replication, the 3 NTR, in particular 3X, stabilizes the RNA and enhances translation both in vitro and in transfected cells =-=(24, 54)-=-. These effects require the binding to the 3 NTR of cellular factors such as PTB, the autoantigen La, or some ribosomal proteins (23, 52, 60). Conflicting data on whether or not the 3 NTR is essenti...

3� nontranslated RNA signals required for replication of hepatitis C virus RNA

by Minkyung Yi, Stanley M. Lemon, Minkyung Yi, Stanley M. Lemon - J , 2003
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Abstract - Cited by 39 (0 self) - Add to MetaCart
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...cannot be excluded, the structure does not appear to be an important determinant of RNA replication. Role of 3�NTR sequences in promoting IRES-directed translation and RNA stability. Since Ito et al. =-=(19)-=- suggested that sequences within the HCV 3�NTR may positively influence the translation-initiating activity of an upstream IRES, it was important to consider whether any of the deletions in the 3�NTR ...

A promoter activity is present in the DNA sequence corresponding to the hepatitis C virus 50 UTR

by Estelle Dumas, Cathy Staedel, Marie Colombat, Rine Reigadas, Rine Chabas, Theâreáse Astier-gin, Annie Cahour, Simon Litvak, Michel Ventura - Nucleic Acids Res , 2003
"... The hepatitis C virus (HCV) 5 ¢ untranslated region (UTR) has been extensively studied with regard to its internal ribosomal entry site (IRES) activity. In this work we present results suggesting the exist-ence of a strong promoter activity carried by the DNA sequence corresponding to the HCV 5 ¢ UT ..."
Abstract - Cited by 22 (4 self) - Add to MetaCart
The hepatitis C virus (HCV) 5 ¢ untranslated region (UTR) has been extensively studied with regard to its internal ribosomal entry site (IRES) activity. In this work we present results suggesting the exist-ence of a strong promoter activity carried by the DNA sequence corresponding to the HCV 5 ¢ UTR. This activity was not detected when the HCV 5 ¢ UTR sequence was replaced by HCV 3 ¢ UTR or poliovirus 5 ¢ UTR sequences. These results were further con®rmed by using bicistronic constructions. We demonstrated the presence of an mRNA initiated in this 5 ¢ UTR sequence and located the initiation site by the 5 ¢ RACE method at nucleotide 67. Furthermore, northern experiments and ¯ow cyto-metry analysis showed the unambiguous activity of such a promoter sequence in stably transfected cells. Our results strongly suggest that the data obtained using bicistronic DNA constructs carrying the HCV 5 ¢ UTR should be analyzed not only at the translational but also at the transcriptional level.
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...ranslation in vitro and in vivo. It has been suggested that this effect involves the polypyrimidine tract binding protein, which is found associated with both the 5¢ and the 3¢ ends of the viral mRNA =-=(8)-=-. Similarly, the ®rst 125 nt of the 5¢ UTR, have been shown to be essential for the replication of the HCV genome (9). Although HCV was identi®ed more than 10 years ago (10), a cellular model system a...

Secondary structure and hybridization accessibility of the hepatitis C virus negative strand RNA 5 0 -terminus

by Robert M. Smith, Cherie M. Walton, Catherine H. Wu, George Y. Wu, J. Virol, Robert M. Smith, Cherie M. Walton, Catherine H. Wu, George Y. Wu - J. Viral Hepat , 2004
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...e strand reportedly plays an analogous role in positive-strand RNA synthesis (25, 36, 39). The binding of HCV 3� termini to various host proteins may exert subtle effects on IRES-mediated translation =-=(16, 23, 34, 55)-=- or protect viral transcripts from degradation by cytoplasmic RNases (15, 48, 49). The replicative and protein-binding functions of heteropolymeric regions in the HCV 3� termini are, in many instances...

Cap-Independent Translational Enhancement of Turnip Crinkle Virus Genomic and Subgenomic RNAs

by Subgenomic Rnas, Feng Qu, T. Jack Morris, Feng Qu, T. Jack Morris , 1999
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...imilarity to a pyrimidine-rich domain identified in hepatitis C virus (HCV) (Fig. 8B) that is implicated in specific high-affinity binding to a host factor called polypyrimidine tract binding protein =-=(20)-=-. The HCV genome is also a single-stranded, plus-sense RNA which is neither capped nor 3�-polyadenylated. In this example, binding of polypyrimidine tract binding protein to the 3� UTR (X region) of H...

IRES-driven translation is stimulated separately by the FMDV 39-NCR and poly(A) sequences. Nucleic Acids Res

by Sonia Loâ Pez De Quinto, Margarita Saâiz, Diana De La Morena, Francisco Sobrino , 2002
"... The 3 ¢ end region of foot-and-mouth disease virus (FMDV) consists of two distinct elements, a 90 nt untranslated region (3¢-NCR) and a poly(A) tract. Removal of either the poly(A) tract or both the 3¢-NCR and the poly(A) tract abrogated infectivity in susceptible cells in the context of a full-leng ..."
Abstract - Cited by 13 (3 self) - Add to MetaCart
The 3 ¢ end region of foot-and-mouth disease virus (FMDV) consists of two distinct elements, a 90 nt untranslated region (3¢-NCR) and a poly(A) tract. Removal of either the poly(A) tract or both the 3¢-NCR and the poly(A) tract abrogated infectivity in susceptible cells in the context of a full-length cDNA clone. We have addressed the question of whether the impairment of RNA infectivity is related to defects at the translation level using a double approach. First, compared to the full-length viral RNA, removal of the 3 ¢ sequences reduced the ef®ciency of translation in vitro. Secondly, a stimulatory effect of the 3 ¢ end sequences on IRESdependent translation was found in vivo using bicistronic constructs. RNAs carrying the FMDV 3¢ end sequences linked to the second cistron showed a signi®cant stimulation of IRES-dependent translation, whereas cap-dependent translation was not affected. Remarkably, IRES-dependent stimulation exerted by the poly(A) tract or the 3¢-NCR seems to be the result of two separate events, as the 3¢-NCR alone enhanced IRES activity on its own. Under conditions of FMDV Lb protease-induced translation shut-off, the stimulation of IRES activity reached values above 6-fold in living cells. A northern blot analysis indicated that IRES stimulation was not the consequence of a change in the stability of the bicistronic RNA produced in transfected cells. Analysis of the RNA-binding proteins interacting with a mixture of 3 ¢ end and IRES probes showed an additive pattern. Altogether, our results strongly suggest that individual signals in the viral 3 ¢ end ensure stimulation of FMDV translation.
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...r data have underscored a new role for FMDV 3¢-NCR sequences in the stimulation of IRES-dependent translation. The X region of the 3¢-NCR of HCV has also been reported to enhance HCV IRES translation =-=(6,14,15)-=-. However, a downregulatory effect was observed when the entire 3¢-untranslated region was present in full-length cDNA clones (39). Likewise, suppression of translation has been reported in chimeric R...

The hepatitis C virus RNA 3 ′ - untranslated region strongly enhances translation directed by the internal ribosome entry site

by Yutong Song, Peter Friebe, Eleni Tzima, Ralf Bartenschlager, Michael Niepmann, Yutong Song, Peter Friebe, Eleni Tzima, Christiane Jünemann, Ralf Bartenschlager, Michael Niepmann - Journal of Virology , 2006
"... These include: This article cites 59 articles, 40 of which can be accessed free at: ..."
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...anslation, obtained either in vitro, in cell culture, or in transfected livers of mice. In some studies, a positive influence of 3�-UTR sequences (sometimes comprising only the 3� X region) was shown =-=(19, 20, 34, 35)-=-. One study reported an inhibitory effect of the 3�-UTR (37), whereas other reports claimed that there Downloaded from http://jvi.asm.org/ on February 21, 2013 by PENN STATE UNIV 1157911580 SONG ET A...

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