Automated classification of RNA 3D motifs and the RNA 3D Motif Atlas

Abstract

The analysis of atomic-resolution RNA three-dimensional (3D) structures reveals that many internal and hairpin loops are modular, recurrent, and structured by conserved non-Watson-Crick base pairs. Structurally similar loops define RNA 3D motifs that are conserved in homologous RNA molecules, but can also occur at nonhomologous sites in diverse RNAs, and which often vary in sequence. To further our understanding of RNA motif structure and sequence variability and to provide a useful resource for structure modeling and prediction, we present a new method for automated classification of internal and hairpin loop RNA 3D motifs and a new online database called the RNA 3D Motif Atlas. To classify the motif instances, a representative set of internal and hairpin loops is automatically extracted from a nonredundant list of RNA-containing PDB files. Their structures are compared geometrically, all-against-all, using the FR3D program suite. The loops are clustered into motif groups, taking into account geometric similarity and structural annotations and making allowance for a variable number of bulged bases. The automated procedure that we have implemented identifies all hairpin and internal loop motifs previously described in the literature. All motif instances and motif groups are assigned unique and stable identifiers and are made available in the RNA 3D Motif Atlas (http://rna.bgsu.edu/motifs), which is automatically updated every four weeks. The RNA 3D Motif Atlas provides an interactive user interface for exploring motif diversity and tools for programmatic data access.

Predicting RNA 3D structure using a coarse-grain helix-centered model

“…The inclusion of predicted local structural motifs (Lescoute et al 2005;Sarver et al 2008;Petrov et al 2013;Theis et al 2013) provides an immediate avenue for the improvement of the prediction quality. Information about the extended secondary structure (Höner zu Siederdissen et al 2011) of a sequence could provide a more fine-grain partitioning of the statistics used in generating the proposal distribution.…”

The RNA 3D Motif Atlas: Computational methods for extraction, organization and evaluation of RNA motifs

“…Next, the pipeline gathers all HL and IL from representative structures in the 4.0Å NR set and validates each loop as described in Petrov et al [1]. The 4.0Å NR sets are based largely on structures determined by X-ray crystallography.…”

“…In the Materials and Methods section we discuss the selection of a target set of reliable, non-redundant (NR) RNA 3D structure files for analysis. We also provide computational details of methods currently used to build and maintain the RNA 3D Motif Atlas, see http://rna.bgsu.edu/rna3dhub/motifs [1]. In the Theory section, we provide the conceptual framework used to annotate, classify and cluster RNA motifs into coherent groups intended for downstream bioinformatic analysis.…”

Reverse Watson-Crick purine-purine base pairs — the Sharp-turn motif and other structural consequences in functional RNAs

“…Recent progress in RNA-based therapeutics 2 including RNA vaccination therapy 3 and successful application of RNA based technologies in plant 4 and animal agriculture 5 have highlighted the importance of developing an overall understanding of the sequence-structure-function relationships in RNA. Despite numerous scientific investigations exploring the sequence-structure [6][7][8][9] and structure-function [10][11][12] spaces for RNA, a comprehensive picture similar to those for protein or DNA is yet to evolve 1,13,14 . RNA achieves the remarkable structural complexity and fascinating functional diversity similar to proteins with only four different building blocks (nucleotides), instead of twenty physicochemically different amino acids as present in proteins.…”