Abstract
BackgroundDiscrete RNA structures such as cis-acting replication elements (cre) in the coding region of RNA virus genomes create characteristic suppression of synonymous site variability (SSSV). Different phylogenetic methods have been developed to predict secondary structures in RNA viruses, for high-resolution thermodynamic scanning and for detecting SSSV. These approaches have been successfully in predicting cis-acting signals in different members of the family Picornaviridae and Caliciviridae. In order to gain insight into the identification of cis-acting signals in viruses whose mechanisms of replication are currently unknown, we performed a phylogenetic analysis of complete genome sequences from 49 Human Norovirus (NoV) strains.FindingsThe complete coding sequences of NoV ORF1 were obtained from the DDBJ database and aligned. Shannon entropy calculations and RNAalifold consensus RNA structure prediction identified a discrete, conserved, invariant sequence region with a characteristic AAACG cre motif at positions 240 through 291 of the RNA dependant RNA polymerase (RdRp) sequence (relative to strain [EMBL:EU794713]). This sequence region has a high probability to conform a stem-loop.ConclusionA new predicted stem-loop has been identified near the 5' end of the RdRp of Human NoV genome. This is the same location recently reported for Hepatovirus cre stem-loop.
Highlights
Discrete RNA structures such as cis-acting replication elements in the coding region of RNA virus genomes create characteristic suppression of synonymous site variability (SSSV)
Internal base pairing that creates stem-loops and other RNA structures places constraints on sequence variability in bases required for structure formation in the genome of RNA viruses
The Hepatitis C virus (HCV) genome has a marked suppression of synonymous codon variability within several evolutionary conserved stemloops in the core and NS5B coding regions that demonstrate their role in virus replication [1,2,3]
Summary
Internal base pairing that creates stem-loops and other RNA structures places constraints on sequence variability in bases required for structure formation in the genome of RNA viruses. BMC Research Notes 2009, 2:176 http://www.biomedcentral.com/1756-0500/2/176 ble genome regions for an in-depth experimental analysis allowing establishing the role of the identified secondary RNA structures in translation or replication This approach has permitted to raise the hypothesis that when SSSV (i.e. highly conserved synonymous sites in a RNA virus genome sequence alignment) takes place in a sequence region with a high probability of conforming a secondary structure (i.e. high probability of base pairing to generate a stable stem-loop), a cis-acting signal can be identified. It is possible that the predicted stem-loop identified near the 5' end of the NoV RdRp coding region, which share a cre-like sequence motif with members of the family Picornaviridae [10], will be capable to perform the uridylylation of VPg. If that is the case, this will permit VPg to act as a primer for the synthesis of the minus strand RNA, in agreement with the results outlined above [30]
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