Abstract
Genetic algorithm-based RNA secondary structure prediction was used in combination with comparative sequence analysis to construct models of folding for the distal part of the 3'-untranslated region of flaviviruses belonging to four serological groups. Elements of RNA secondary structure that are preserved among all the flaviviruses studied were revealed, despite the high degree of sequence divergence between them. At the same time, structural elements were observed that distinguish members of different serological groups and, in particular, a region of remarkable structural divergence between the tick-borne and mosquito-borne flaviviruses was found. Application of the genetic algorithm also revealed that the 3'-terminus of flaviviral genomic RNA may take on alternative conformations, which are not observed in the 3'-terminus of complementary minus strand RNA. These alternative folding patterns may have roles in the regulation of transcription and translation initiation and in the switch between them.
Full Text
The Full Text of this article is available as a PDF (157.8 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Battiste J. L., Tan R., Frankel A. D., Williamson J. R. Binding of an HIV Rev peptide to Rev responsive element RNA induces formation of purine-purine base pairs. Biochemistry. 1994 Mar 15;33(10):2741–2747. doi: 10.1021/bi00176a001. [DOI] [PubMed] [Google Scholar]
- Blackwell J. L., Brinton M. A. BHK cell proteins that bind to the 3' stem-loop structure of the West Nile virus genome RNA. J Virol. 1995 Sep;69(9):5650–5658. doi: 10.1128/jvi.69.9.5650-5658.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brinton M. A., Fernandez A. V., Dispoto J. H. The 3'-nucleotides of flavivirus genomic RNA form a conserved secondary structure. Virology. 1986 Aug;153(1):113–121. doi: 10.1016/0042-6822(86)90012-7. [DOI] [PubMed] [Google Scholar]
- Calisher C. H., Karabatsos N., Dalrymple J. M., Shope R. E., Porterfield J. S., Westaway E. G., Brandt W. E. Antigenic relationships between flaviviruses as determined by cross-neutralization tests with polyclonal antisera. J Gen Virol. 1989 Jan;70(Pt 1):37–43. doi: 10.1099/0022-1317-70-1-37. [DOI] [PubMed] [Google Scholar]
- Chambers T. J., Hahn C. S., Galler R., Rice C. M. Flavivirus genome organization, expression, and replication. Annu Rev Microbiol. 1990;44:649–688. doi: 10.1146/annurev.mi.44.100190.003245. [DOI] [PubMed] [Google Scholar]
- Cleaves G. R., Ryan T. E., Schlesinger R. W. Identification and characterization of type 2 dengue virus replicative intermediate and replicative form RNAs. Virology. 1981 May;111(1):73–83. doi: 10.1016/0042-6822(81)90654-1. [DOI] [PubMed] [Google Scholar]
- Coia G., Parker M. D., Speight G., Byrne M. E., Westaway E. G. Nucleotide and complete amino acid sequences of Kunjin virus: definitive gene order and characteristics of the virus-specified proteins. J Gen Virol. 1988 Jan;69(Pt 1):1–21. doi: 10.1099/0022-1317-69-1-1. [DOI] [PubMed] [Google Scholar]
- Grange T., Bouloy M., Girard M. Stable secondary structures at the 3'-end of the genome of yellow fever virus (17 D vaccine strain). FEBS Lett. 1985 Aug 19;188(1):159–163. doi: 10.1016/0014-5793(85)80895-4. [DOI] [PubMed] [Google Scholar]
- Gultyaev A. P., van Batenburg F. H., Pleij C. W. The computer simulation of RNA folding pathways using a genetic algorithm. J Mol Biol. 1995 Jun 30;250(1):37–51. doi: 10.1006/jmbi.1995.0356. [DOI] [PubMed] [Google Scholar]
- Gultyaev A. P., van Batenburg F. H., Pleij C. W. The influence of a metastable structure in plasmid primer RNA on antisense RNA binding kinetics. Nucleic Acids Res. 1995 Sep 25;23(18):3718–3725. doi: 10.1093/nar/23.18.3718. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hahn C. S., Hahn Y. S., Rice C. M., Lee E., Dalgarno L., Strauss E. G., Strauss J. H. Conserved elements in the 3' untranslated region of flavivirus RNAs and potential cyclization sequences. J Mol Biol. 1987 Nov 5;198(1):33–41. doi: 10.1016/0022-2836(87)90455-4. [DOI] [PubMed] [Google Scholar]
- Mandl C. W., Holzmann H., Kunz C., Heinz F. X. Complete genomic sequence of Powassan virus: evaluation of genetic elements in tick-borne versus mosquito-borne flaviviruses. Virology. 1993 May;194(1):173–184. doi: 10.1006/viro.1993.1247. [DOI] [PubMed] [Google Scholar]
- Mandl C. W., Kunz C., Heinz F. X. Presence of poly(A) in a flavivirus: significant differences between the 3' noncoding regions of the genomic RNAs of tick-borne encephalitis virus strains. J Virol. 1991 Aug;65(8):4070–4077. doi: 10.1128/jvi.65.8.4070-4077.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marin M. S., Zanotto P. M., Gritsun T. S., Gould E. A. Phylogeny of TYU, SRE, and CFA virus: different evolutionary rates in the genus Flavivirus. Virology. 1995 Feb 1;206(2):1133–1139. doi: 10.1006/viro.1995.1038. [DOI] [PubMed] [Google Scholar]
- Matsuzaki H., Kassavetis G. A., Geiduschek E. P. Analysis of RNA chain elongation and termination by Saccharomyces cerevisiae RNA polymerase III. J Mol Biol. 1994 Jan 28;235(4):1173–1192. doi: 10.1006/jmbi.1994.1072. [DOI] [PubMed] [Google Scholar]
- Poidinger M., Hall R. A., Mackenzie J. S. Molecular characterization of the Japanese encephalitis serocomplex of the flavivirus genus. Virology. 1996 Apr 15;218(2):417–421. doi: 10.1006/viro.1996.0213. [DOI] [PubMed] [Google Scholar]
- Puglisi J. D., Tan R., Calnan B. J., Frankel A. D., Williamson J. R. Conformation of the TAR RNA-arginine complex by NMR spectroscopy. Science. 1992 Jul 3;257(5066):76–80. doi: 10.1126/science.1621097. [DOI] [PubMed] [Google Scholar]
- Rice C. M., Lenches E. M., Eddy S. R., Shin S. J., Sheets R. L., Strauss J. H. Nucleotide sequence of yellow fever virus: implications for flavivirus gene expression and evolution. Science. 1985 Aug 23;229(4715):726–733. doi: 10.1126/science.4023707. [DOI] [PubMed] [Google Scholar]
- Shi P. Y., Brinton M. A., Veal J. M., Zhong Y. Y., Wilson W. D. Evidence for the existence of a pseudoknot structure at the 3' terminus of the flavivirus genomic RNA. Biochemistry. 1996 Apr 2;35(13):4222–4230. doi: 10.1021/bi952398v. [DOI] [PubMed] [Google Scholar]
- Thompson J. D., Higgins D. G., Gibson T. J. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994 Nov 11;22(22):4673–4680. doi: 10.1093/nar/22.22.4673. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wallner G., Mandl C. W., Kunz C., Heinz F. X. The flavivirus 3'-noncoding region: extensive size heterogeneity independent of evolutionary relationships among strains of tick-borne encephalitis virus. Virology. 1995 Oct 20;213(1):169–178. doi: 10.1006/viro.1995.1557. [DOI] [PubMed] [Google Scholar]
- Wengler G., Castle E. Analysis of structural properties which possibly are characteristic for the 3'-terminal sequence of the genome RNA of flaviviruses. J Gen Virol. 1986 Jun;67(Pt 6):1183–1188. doi: 10.1099/0022-1317-67-6-1183. [DOI] [PubMed] [Google Scholar]
- Zanotto P. M., Gould E. A., Gao G. F., Harvey P. H., Holmes E. C. Population dynamics of flaviviruses revealed by molecular phylogenies. Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):548–553. doi: 10.1073/pnas.93.2.548. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zuker M. On finding all suboptimal foldings of an RNA molecule. Science. 1989 Apr 7;244(4900):48–52. doi: 10.1126/science.2468181. [DOI] [PubMed] [Google Scholar]
- van Batenburg F. H., Gultyaev A. P., Pleij C. W. An APL-programmed genetic algorithm for the prediction of RNA secondary structure. J Theor Biol. 1995 Jun 7;174(3):269–280. doi: 10.1006/jtbi.1995.0098. [DOI] [PubMed] [Google Scholar]