RAG: RNA-As-Graphs web resource

Abstract

Background: The proliferation of structural and functional studies of RNA has revealed an increasing range of RNA's structural repertoire. Toward the objective of systematic cataloguing of RNA's structural repertoire, we have recently described the basis of a graphical approach for organizing RNA secondary structures, including existing and hypothetical motifs.

Description: We now present an RNA motif database based on graph theory, termed RAG for RNA-As-Graphs, to catalogue and rank all theoretically possible, including existing, candidate and hypothetical, RNA secondary motifs. The candidate motifs are predicted using a clustering algorithm that classifies RNA graphs into RNA-like and non-RNA groups. All RNA motifs are filed according to their graph vertex number (RNA length) and ranked by topological complexity.

Conclusions: RAG's quantitative cataloguing allows facile retrieval of all classes of RNA secondary motifs, assists identification of structural and functional properties of user-supplied RNA sequences, and helps stimulate the search for novel RNAs based on predicted candidate motifs.

Figure 1

Graphical representations of RNA structures. Secondary structures of P5abc and tRNA(leu) (top row) are represented as both tree (middle) and dual (bottom) graphs. We use corresponding labels S1, S2, etc. for stems and B1, B2, etc. for bulges, loops or junctions; the chain ends (B0) are not represented in dual graphs. In tree graphs, stems are represented as edges or lines (—) and bulges/loops/junctions/chain ends as vertices (◆). In contrast, in dual graphs, bulges/loops/junctions are represented as edges or lines (—) and stems as vertices (◆).

Figure 2

Entries in tree and dual graph libraries. The tree graph (A) and dual graph (B) motifs are ordered according to the vertex number V and the second smallest Laplacian eigenvalue λ₂. Existing (red color), candidate (blue) and hypothetical (black) RNA motifs.

Figure 3

Organization of the RAG database. Information about RNA's topological libraries in RAG is organized hierarchically according to graph motif type (tree or dual), vertex number, library of topologies, and status of topology (existing, candidate, or hypothetical), with hyperlinks to other databases providing sequence, structure, and function data of existing RNAs. The existing RNA topologies are also catalogued according to functional class. Other components of RAG include an RNA Matrix Program for converting a secondary structure into a tree graph and RNA tutorials on concepts and techniques employed.

Figure 4

Searching for structural neighbors of a natural RNA in RAG. The search steps are illustrated using a star-shaped, five-stem tRNA(leu) structure, starting from its sequence to structural neighbors. The search utilizes an RNA folding program, RNA Matrix Program, and archived libraries of topologies.