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A comparative method for finding and folding RNA secondary structures within protein-coding regions

Item Type:Article
Title:A comparative method for finding and folding RNA secondary structures within protein-coding regions
Creators Name:Pedersen, J.S., Meyer, I.M., Forsberg, R., Simmonds, P. and Hein, J.
Abstract: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-D(ECODER), 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-D(ECODER) 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-D(ECODER)'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-D(ECODER) shows a sensitivity similar to the programs M(FOLD), P(FOLD) and RNAALIFOLD. When scanning the entire genomes of HCV and polio virus for structure elements, RNA-D(ECODER)'s results indicate a markedly higher specificity than M(FOLD), P(FOLD) and RNA(ALIFOLD).
Keywords:Codon, Hepacivirus, Molecular Evolution, Nucleic Acid Conformation, Phylogeny, Poliovirus, Proteins, RNA, Sequence Alignment, RNA Sequence Analysis, Software, Stochastic Processes, Viral RNA
Source:Nucleic Acids Research
Publisher:Oxford University Press
Page Range:4925-4936
Date:24 September 2004
Official Publication:https://doi.org/10.1093/nar/gkh839
PubMed:View item in PubMed

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