Introduction

Existing computational methods for RNA secondary-structure prediction tacitly assume RNA to only encode functional RNA structures. However, experimental studies have revealed that some RNA sequences, e.g. compact viral genomes, can simultaneously encode functional RNA structures as well as proteins, and evidence is accumulating that this phenomenon may also be found in Eukaryotes. We here present the first comparative method, called RNA-DECODER, which explicitly takes the known protein-coding context of an RNA-sequence alignment into account in order to predict evolutionarily conserved secondary-structure elements, which may span both coding and non-coding regions. RNA-DECODER employs a stochastic context-free grammar together with a set of carefully devised phylogenetic substitution-models, which can disentangle and evaluate the different kinds of overlapping evolutionary constraints which arise. We show that RNA-DECODER's parameters can be automatically trained to successfully fold known secondary structures within the HCV genome. We scan the genomes of HCV and polio virus for conserved secondary-structure elements, and analyze performance as a function of available evolutionary information. On known secondary structures, RNA-DECODER shows a sensitivity similar to the programs MFOLD, PFOLD and RNAALIFOLD. When scanning the entire genomes of HCV and polio virus for structure elements, RNA-DECODER's results indicate a markedly higher specificity than MFOLD, PFOLD and RNAALIFOLD.

Publications

  1. A comparative method for finding and folding RNA secondary structures within protein-coding regions.
    Cite this
    Pedersen JS, Meyer IM, Forsberg R, Simmonds P, Hein J, 2004-01-01 - Nucleic acids research
  2. An evolutionary model for protein-coding regions with conserved RNA structure.
    Cite this
    Pedersen JS, Forsberg R, Meyer IM, Hein J, 2004-10-01 - Molecular biology and evolution

Credits

  1. Jakob Skou Pedersen
    Developer

    Bioinformatics Research Center, Department of Ecology and Genetics

  2. Irmtraud Margret Meyer
    Developer

  3. Roald Forsberg
    Developer

  4. Peter Simmonds
    Developer

  5. Jotun Hein
    Investigator

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Summary
AccessionBT005678
Tool TypeApplication
Category
PlatformsLinux/Unix
TechnologiesC++
User InterfaceTerminal Command Line
Download Count0
Submitted ByJotun Hein