Secondary structure of the 3'-noncoding region of flavivirus genomes: comparative analysis of base pairing probabilities.

The prediction of the complete matrix of base pairing probabilities was applied to the 3' noncoding region (NCR) of flavivirus genomes. This approach identifies not only well-defined secondary structure elements, but also regions of high structural flexibility. Flaviviruses, many of which are important human pathogens, have a common genomic organization, but exhibit a significant degree of RNA sequence diversity in the functionally important 3'-NCR. We demonstrate the presence of secondary structures shared by all flaviviruses, as well as structural features that are characteristic for groups of viruses within the genus reflecting the established classification scheme. The significance of most of the predicted structures is corroborated by compensatory mutations. The availability of infectious clones for several flaviviruses will allow the assessment of these structural elements in processes of the viral life cycle, such as replication and assembly.

[1]  N. Kato,et al.  Structure of the 3' terminus of the hepatitis C virus genome , 1996, Journal of virology.

[2]  J. Thompson,et al.  CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. , 1994, Nucleic acids research.

[3]  E. G. Westaway,et al.  Completion of Kunjin virus RNA sequence and recovery of an infectious RNA transcribed from stably cloned full-length cDNA , 1994, Journal of virology.

[4]  M. Brinton,et al.  The 3'-nucleotides of flavivirus genomic RNA form a conserved secondary structure. , 1986, Virology.

[5]  P. Hogeweg,et al.  Pattern analysis of RNA secondary structure similarity and consensus of minimal-energy folding. , 1989, Journal of molecular biology.

[6]  M. Zuker,et al.  "Well-determined" regions in RNA secondary structure prediction: analysis of small subunit ribosomal RNA. , 1995, Nucleic acids research.

[7]  Walter Fontana,et al.  Fast folding and comparison of RNA secondary structures , 1994 .

[8]  W D Wilson,et al.  Evidence for the existence of a pseudoknot structure at the 3' terminus of the flavivirus genomic RNA. , 1996, Biochemistry.

[9]  C. Ehresmann,et al.  Functional sites in the 5' region of human immunodeficiency virus type 1 RNA form defined structural domains. , 1993, Journal of molecular biology.

[10]  M. Zuker,et al.  Structural analysis by energy dot plot of a large mRNA. , 1993, Journal of molecular biology.

[11]  P. Schuster,et al.  Statistics of RNA secondary structures , 1993, Biopolymers.

[12]  Peter F. Stadler,et al.  Knowledge Discovery in RNA Sequence Families of HIV Using Scalable Computers , 1996, KDD.

[13]  M. Bouloy,et al.  Stable secondary structures at the 3'‐end of the genome of yellow fever virus (17 D vaccine strain) , 1985, FEBS letters.

[14]  K V Brock,et al.  5' and 3' untranslated regions of pestivirus genome: primary and secondary structure analyses. , 1993, Nucleic acids research.

[15]  L. Ping,et al.  Secondary structure of the 5' nontranslated regions of hepatitis C virus and pestivirus genomic RNAs. , 1992, Nucleic acids research.

[16]  H. Sumiyoshi,et al.  Infectious Japanese encephalitis virus RNA can be synthesized from in vitro-ligated cDNA templates , 1992, Journal of virology.

[17]  J. McCaskill.  The equilibrium partition function and base pair binding probabilities for RNA secondary structure , 1990, Biopolymers.

[18]  J. H. Strauss,et al.  Conserved elements in the 3' untranslated region of flavivirus RNAs and potential cyclization sequences. , 1987, Journal of molecular biology.

[19]  J. F. Atkins,et al.  Nucleotide sequence of a single-stranded RNA phage from Pseudomonas aeruginosa: kinship to coliphages and conservation of regulatory RNA structures. , 1995, Virology.

[20]  M. Huynen,et al.  Assessing the reliability of RNA folding using statistical mechanics. , 1997, Journal of molecular biology.

[21]  M. Bray,et al.  Infectious RNA transcribed from stably cloned full-length cDNA of dengue type 4 virus. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[22]  D. Turner,et al.  Improved free-energy parameters for predictions of RNA duplex stability. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[23]  Alan S. Perelson,et al.  Base Pairing Probabilities in a Complete HIV-1 RNA , 1996, J. Comput. Biol..

[24]  A. Gregoriades,et al.  Assessing the reliability of socio‐technical systems , 2002 .

[25]  C. Pleij,et al.  The computer simulation of RNA folding pathways using a genetic algorithm. , 1995, Journal of molecular biology.

[26]  M. Brinton,et al.  BHK cell proteins that bind to the 3' stem-loop structure of the West Nile virus genome RNA , 1995, Journal of virology.

[27]  C. Biebricher,et al.  The role of RNA structure in RNA replication , 1994 .

[28]  C. Rice,et al.  Transcription of infectious yellow fever RNA from full-length cDNA templates produced by in vitro ligation. , 1989, The New biologist.

[29]  G. Wengler,et al.  Analysis of structural properties which possibly are characteristic for the 3'-terminal sequence of the genome RNA of flaviviruses. , 1986, The Journal of general virology.

[30]  David Sankoff,et al.  RNA secondary structures and their prediction , 1984 .

[31]  C. Mandl,et al.  Infectious cDNA clones of tick-borne encephalitis virus European subtype prototypic strain Neudoerfl and high virulence strain Hypr. , 1997, The Journal of general virology.

[32]  Paulien Hogeweg,et al.  Energy directed folding of RNA sequences , 1984, Nucleic Acids Res..