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Bioinformatic and physical characterizations of genome-scale ordered RNA structure in mammalian RNA viruses
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Davis, M. (Matthew), Sagan, Selena M., Pezacki, John P., Evans, David J. and Simmonds, Peter (2008) Bioinformatic and physical characterizations of genome-scale ordered RNA structure in mammalian RNA viruses. Journal of Virology, Vol.82 (No.23). pp. 11824-11836. doi:10.1128/JVI.01078-08
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Official URL: http://dx.doi.org/10.1128/JVI.01078-08
Abstract
By the analysis of thermodynamic RNA secondary structure predictions, we previously obtained evidence for evolutionarily conserved large-scale ordering of RNA virus genomes (P. Simmonds, A. Tuplin, and D.J. Evans, RNA 10: 1337-1351, 2004). Genome-scale ordered RNA structure (GORS) was widely distributed in many animal and plant viruses, much greater in extent than RNA structures required for viral translation or replication, but in mammalian viruses was associated with host persistence. To substantiate the existence of large-scale RNA structure differences between viruses, a large set of alignments of mammalian RNA viruses and rRNA sequences as controls were examined by thermodynamic methods (to calculate minimum free energy differences) and by algorithmically independent RNAz and Pfold methods. These methods produced generally concordant results and identified substantial differences in the degrees of evolutionarily conserved, sequence order-dependent RNA secondary structure between virus genera and groups. A probe hybridization accessibility assay was used to investigate the physical nature of GORS. Transcripts of hepatitis C virus (HCV), hepatitis G virus/GB virus-C (HGV/GBV-C), and murine norovirus, which are predicted to be structured, were largely inaccessible to hybridization in solution, in contrast to the almost universal binding of probes to a range of unstructured virus transcripts irrespective of G + C content. Using atomic force microscopy, HCV and HGV/GBV-C RNA was visualized as tightly compacted prolate spheroids, while under the same experimental conditions the predicted unstructured poliovirus and rubella virus RNA were pleomorphic and had extensively single-stranded RNA on deposition. Bioinformatic and physical characterization methods both identified fundamental differences in the configurations of viral genomic RNA that may modify their interactions with host cell defenses and their ability to persist.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Subjects: | Q Science > QP Physiology Q Science > QR Microbiology > QR355 Virology |
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) > Biological Sciences ( -2010) | ||||
| Library of Congress Subject Headings (LCSH): | RNA -- Structure, RNA viruses, Genomics, Bioinformatics | ||||
| Journal or Publication Title: | Journal of Virology | ||||
| Publisher: | American Society for Microbiology | ||||
| ISSN: | 0022-538X | ||||
| Official Date: | December 2008 | ||||
| Dates: |
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| Volume: | Vol.82 | ||||
| Number: | No.23 | ||||
| Number of Pages: | 13 | ||||
| Page Range: | pp. 11824-11836 | ||||
| DOI: | 10.1128/JVI.01078-08 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access | ||||
| Funder: | Wellcome Trust (London, England) |
Data sourced from Thomson Reuters' Web of Knowledge
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