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

Anton I Petrov,Craig L Zirbel,Neocles B Leontis

doi:10.1261/rna.039438.113

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.

Highlights

We describe a new method for automated classification of internal and hairpin loop RNA three-dimensional (3D) motifs found in RNA structures deposited in PDB, and a new online resource called the RNA 3D Motif Atlas, which presents the results of the motif classification
If the overlap between the motif groups from the new and previous releases is less than two-thirds of the sizes of either group, a new id is created (Fig. 4A,B)
We use symbolic annotations of pairwise interactions only to separate motif instances annotated with different base-pair types into different motif groups, because different base-pair families have different isostericity rules and can be expected to have different patterns of sequence variability (Stombaugh et al 2009)

Summary

Introduction

We describe a new method for automated classification of internal and hairpin loop RNA three-dimensional (3D) motifs found in RNA structures deposited in PDB, and a new online resource called the RNA 3D Motif Atlas, which presents the results of the motif classification. The RNA 3D Motif Atlas is automatically and regularly updated and can be accessed at http://rna.bgsu.edu/ motifs. “RNA 3D motifs” are conceived broadly as “well-defined geometric arrangements of interacting nucleotides.”. RNA base pairs and other pairwise interactions meet the definition but are better thought of as submotifs, building blocks of larger motifs. Quadruples, Uand S-turns, and UA handles are submotifs as well (Jaeger et al 2009; Abu Almakarem et al 2012; Agarwal et al.2012). RNA helices are ubiquitous and well-characterized RNA motifs, and are not the focus of this paper

Methods

Results

Discussion

Conclusion