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RNA. 2008 November; 14(11): 2274–2289.
doi: 10.1261/rna.853208.
PMCID: PMC2578864
Analysis and classification of RNA tertiary structures
Mira Abraham,1 Oranit Dror,1 Ruth Nussinov,2,3 and Haim J. Wolfson1
1School of Computer Science, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 69978, Israel
2Sackler Institute of Molecular Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
3Basic Research Program, SAIC-Frederick, Inc., Center for Cancer Research Nanobiology Program NCI-Frederick, Frederick, Maryland 21702, USA
Reprint requests to: Haim J. Wolfson, School of Computer Science, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 69978, Israel; e-mail: wolfson/at/post.tau.ac.il; fax: 972-3-640 6476.
Received October 10, 2007; Accepted July 5, 2008.
Abstract
There is a fast growing interest in noncoding RNA transcripts. These transcripts are not translated into proteins, but play essential roles in many cellular and pathological processes. Recent efforts toward comprehension of their function has led to a substantial increase in both the number and the size of solved RNA structures. With the aim of addressing questions relating to RNA structural diversity, we examined RNA conservation at three structural levels: primary, secondary, and tertiary structure. Additionally, we developed an automated method for classifying RNA structures based on spatial (three-dimensional [3D]) similarity. Applying the method to all solved RNA structures resulted in a classified database of RNA tertiary structures (DARTS). DARTS embodies 1333 solved RNA structures classified into 94 clusters. The classification is hierarchical, reflecting the structural relationship between and within clusters. We also developed an application for searching DARTS with a new structure. The search is fast and its performance was successfully tested on all solved RNA structures since the creation of DARTS. A user-friendly interface for both the database and the search application is available online. We show intracluster and intercluster similarities in DARTS and demonstrate the usefulness of the search application. The analysis reveals the current structural repertoire of RNA and exposes common global folds and local tertiary motifs. Further study of these conserved substructures may suggest possible RNA domains and building blocks. This should be beneficial for structure prediction and for gaining insights into structure–function relationships.
Keywords: noncoding RNA, structural classification of RNA, alignment of RNA tertiary (3D) structures, 3D database search, edit distance of RNA secondary (2D) structures, RNA sequence comparison