2002
DOI: 10.1017/s1355838202554066
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Thermodynamic and phylogenetic prediction of RNA secondary structures in the coding region of hepatitis C virus

Abstract: The existence and functional importance of RNA secondary structure in the replication of positive-stranded RNA viruses is increasingly recognized. We applied several computational methods to detect RNA secondary structure in the coding region of hepatitis C virus (HCV), including thermodynamic prediction, calculation of free energy on folding, and a newly developed method to scan sequences for covariant sites and associated secondary structures using a parsimony-based algorithm. Each of the prediction methods … Show more

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Cited by 113 publications
(141 citation statements)
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“…4). The data presented here, together with the location of the cre in the coding region in most picornaviruses and with thermodynamic and phylogenetic evidence for RNA structures in other viruses, highlight the potential significance of RNA structures in coding regions (Mathews et al, 1999;Tuplin et al, 2002). Predicted structures in caliciviruses have been tested recently and their disruption affects virus replication .…”
Section: Discussionmentioning
confidence: 58%
See 1 more Smart Citation
“…4). The data presented here, together with the location of the cre in the coding region in most picornaviruses and with thermodynamic and phylogenetic evidence for RNA structures in other viruses, highlight the potential significance of RNA structures in coding regions (Mathews et al, 1999;Tuplin et al, 2002). Predicted structures in caliciviruses have been tested recently and their disruption affects virus replication .…”
Section: Discussionmentioning
confidence: 58%
“…SimPlot version 3.2 (Lole et al, 1999), using the Kimura two-parameter technique, was used to investigate possible recombination events. Synonymous codon variability was determined, using the Simmonics sequence editor (Tuplin et al, 2002), by measuring mean pair-wise distances at each codon position of the 17 complete sequences and 61 3D sequences. The analysis was restricted to codons where the encoded amino acids were the same in all sequences.…”
mentioning
confidence: 99%
“…Most HCV isolates are therefore unlikely to support a frameshift, even within core codons 8-11. HCV-1 codons 8-11 contain the sequences A AAA AAA and A AAA AAC, which are consistent with the consensus ribosomal frameshift signal X XXY YYZ (X,Y,Z: any nucleotide), and are followed by conserved RNA stem-loops {SL47, SL87 (14,25,26)}. Choi et al (23) demonstrated the importance of the region predicted to form SL47 and SL87 (codons 15-53) in Figure 1.…”
Section: Alternative Forms Of Core11 Proteins Trans-lated By Frameshimentioning
confidence: 59%
“…Moreover, recent studies with the highly efficient cell culture HCV infection system based on JFH1 and chimeric H77/JFH1 genomes have shown that the insertion of nonsense mutations into the core11 ORF has no effect on viral replication, the production of viral proteins or the release of infectious virus particles (84). By contrast, the integrity of the RNA structure embedded in the core11 sequence has been shown to be important in that mutations designed to disrupt the predicted highly conserved RNA stem-loops SL47 (nt 388-425) and SL87 (nt 428-508) (14,25,26) impair HCV genome translation (84) and viral proliferation in cell culture and in vivo, in both HCV-infected chimpanzees and mice xenografted with primary human hepatocytes (84,85).…”
Section: Functional Properties Of Core11 Proteinsmentioning
confidence: 99%
“…There are, however, a number of wellknown exceptions to this rule. A variety of conserved secondary structure elements have been detected in computational surveys of single stranded RNA virus genomes [165,406,405,402,439]. A comparative study of 28 different species [195] provides evidence for wide-spread selection for local secondary structures in mRNAs, in particular in eubacteria.…”
Section: Rna Structures In Coding Regionsmentioning
confidence: 99%