The PETfold and PETcofold web servers for intra- and intermolecular structures of multiple RNA sequences

Abstract

The function of non-coding RNA genes largely depends on their secondary structure and the interaction with other molecules. Thus, an accurate prediction of secondary structure and RNA-RNA interaction is essential for the understanding of biological roles and pathways associated with a specific RNA gene. We present web servers to analyze multiple RNA sequences for common RNA structure and for RNA interaction sites. The web servers are based on the recent PET (Probabilistic Evolutionary and Thermodynamic) models PETfold and PETcofold, but add user friendly features ranging from a graphical layer to interactive usage of the predictors. Additionally, the web servers provide direct access to annotated RNA alignments, such as the Rfam 10.0 database and multiple alignments of 16 vertebrate genomes with human. The web servers are freely available at: http://rth.dk/resources/petfold/

Figure 1.

The PETfold output for the microRNA lin-4 based on the sequence alignment from Rfam 10.0: (a)–(d) are seed sequences without paralogs and (e)–(f) are seed sequences without paralogs and Drosophila melanogaster. The output consists of a phylogenetic tree (a), the respective input alignment with indication of the sequence conservation and the predicted RNA structure in dot-bracket format and pairing reliabilities (b and e), the predicted RNA structure (c and f), and finally the dotplot with base pair reliabilities in the upper left triangle (size of squares is linear correlated to reliabilities) and MEA-structure in lower right triangle (d). The vertical and horizontal lines stand for base indices dividable by 10. In (b,c,e,f) compensatory mutations supporting the consensus structure are marked by the Vienna RNA coloring schema.

Figure 2.

The PET(co)fold output for the antisense RNA FinP regulation of the 5′-UTR of the major F-plasmid transcriptional activator TraJ based on the sequence alignment without paralogs from Rfam 10.0: (a) the dotplot of FinP with base pair reliabilities in upper left triangle and MEA-structure in lower right triangle produced by PETfold; (b) the dotplot of TraJ produced by PETfold; (c) the concatenated Rfam seed alignments with sequence conservation indicated, the PETcofold predicted structure in dot-bracket format and base paired reliabilities; (d) the PETcofold predicted RNA binding structure. (a) and (b) show the output produced by the PETfold web server and (c) and (d) show the output produced by the PETcofold web server. Intra-molecular pairing is denoted by round brackets in (c) and arcs in (d) and inter-molecular pairing is denoted by curly brackets in (c) and straight lines between both sequences in (d).