Secondary Structure of the 3'-Non-Coding 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' non-coding 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 pathogenes, 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 to assess the involvement of these structures in specific processes of the viral life cycle, such as replication and assembly.