Source:http://linkedlifedata.com/resource/pubmed/id/18559926
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
Pt 7
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pubmed:dateCreated |
2008-6-18
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pubmed:abstractText |
Since the first report of frameshifting in HCV-1, its sequence has been the paradigm for examining the mechanism that directs alternative translation of the hepatitis C virus (HCV) genome. The region encoding the core protein from this strain contains a cluster of 10 adenines at codons 8-11, which is thought to direct programmed ribosomal frameshifting (PRF), but formal evidence for this process has not been established unequivocally. To identify the mechanisms of frameshifting, this study used a bicistronic dual luciferase reporter system in a coupled transcription/translation in vitro assay. This approach revealed +1 as well as -1 frameshifting, whereas point mutations, selectively introduced between codons 8 and 11, demonstrated that PRF did not readily account for frameshifting in strain HCV-1. Sequence analysis of cDNAs derived from RNA transcribed by T7 RNA polymerase in the dual luciferase reporter system, as well as in both a subgenomic replicon and an infectious clone derived from strain JFH1, identified additions and deletions of adenines between codons 8 and 11 due to transcriptional slippage (TS). Moreover, RNA isolated from cells infected with virus generated by JFH1 containing the A-rich tract also contained heterogeneity in the adenine sequence, strongly suggesting TS by the NS5B viral polymerase. These findings have important implications for insight into frameshifting events in HCV-1 and demonstrate for the first time the involvement of transcriptional slippage in this recoding event.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0022-1317
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
89
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1569-78
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pubmed:meshHeading |
pubmed-meshheading:18559926-DNA, Complementary,
pubmed-meshheading:18559926-Frameshifting, Ribosomal,
pubmed-meshheading:18559926-Genes, Reporter,
pubmed-meshheading:18559926-Hepacivirus,
pubmed-meshheading:18559926-Luciferases,
pubmed-meshheading:18559926-Sequence Analysis, DNA,
pubmed-meshheading:18559926-Transcription, Genetic,
pubmed-meshheading:18559926-Viral Core Proteins
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pubmed:year |
2008
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pubmed:articleTitle |
Transcriptional slippage prompts recoding in alternate reading frames in the hepatitis C virus (HCV) core sequence from strain HCV-1.
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pubmed:affiliation |
IBCP (Institut de Biologie et Chimie des Protéines), CNRS, UMR 5086, Université de Lyon, IFR 128, 7 passage du Vercors, F-69367 Lyon, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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