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dc.contributor.authorTuplin, Andrewen
dc.date.accessioned2018-01-31T11:39:07Z
dc.date.available2018-01-31T11:39:07Z
dc.date.issued2004en
dc.identifier.urihttp://hdl.handle.net/1842/27558
dc.description.abstracten
dc.description.abstractThe existence and functional importance of RNA secondary structure in the replication of positive-stranded RNA viruses is increasingly recognised. In this thesis several computational methods to detect RNA secondary structure in the coding regions of hepatitis C virus (HCV), hepatitis G virus (HGV)/GB virus C (GBV-C) and related viruses have been used. These include thermodynamic prediction of folding free energies (FFEs), evolutionary conservation of minimum energy structures between virus genotypes, suppression of synonymous variability and analysis of covariant and semi covariant substitutions in thermodynamically favoured structures. Each of the predictive methods provided evidence for conserved RNA secondary structure in the core and NS5B encoding regions of HCV and throughout the entire coding region of HGV/GBV-C.en
dc.description.abstractPositions in the HCV genome with predicted RNA structure localise precisely to regions of marked suppression of variability at synonymous sites, indicating that RNA structure constrains sequence change at what are generally regarded as phenotypically neutral sites. Combining these methods, the computational data obtained in this thesis demonstrates the existence of at least ten conserved stem loop structures within the NS5B coding region and three in that coding for the core protein both within the coding region of HCV. Analysis of the NS5B coding region and 3' untranslated region (3'UTR) of HGV/GBV-C indicates an even greater degree of RNA secondary structure. Remarkably, it appears from analysis of FFEs that extensive RNA secondary structure may exist along the entire length of both the HCV and HGV/GBV-C genomes, a finding with considerable implications for future functional studies.en
dc.description.abstractThe existence of predicted RNA structures in the HCV genome was determined using controlled nuclease mapping of RNA transcripts from the core and NS5B regions under conditions which retained potential long-range RNA interactions. The pattern of cleavage sites of nucleases specific for single and double stranded RNA provided strong experimental support for structures previously predicted in this study. Electron microscopy was also used to directly visualise the RNA folding structure of HGV/GBV-C and provided some evidence for at least four structures within the NS5B coding region and long range RNA folding across the length of the virus genome.en
dc.description.abstractThe degree of structural conservation between diverse HCV and HGV/GBV-C genotypes and related viruses suggests roles in virus replication, and/or RNA packaging for the discrete structures identified in this thesis. Whilst this role and that of the genome wide structure identified is currently not understood the structures predicted in this work are providing a starting point for such functional studies using the HCV replicon.en
dc.publisherThe University of Edinburghen
dc.relation.isreferencedbyAlready catalogueden
dc.subjectAnnexe Thesis Digitisation Project 2017 Block 16en
dc.titlePrediction of RNA secondary structure in hepatitis C and related virusesen
dc.typeThesis or Dissertationen
dc.type.qualificationlevelen
dc.type.qualificationnamePhD Doctor of Philosophyen


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