Computational Methods for Tertiary RNA Folding and Novel RNA Design


Funded by the National Science Foundation

EMT Award CF-0727001


Project participants

Tamar Schlick (PI)

Hin Hark Gan

Christian Laing

Yurong Xin

Namhee Kim

Guilio Quarta

Segun Jung

Joseph Izzo

Abdul Qadeer Iqbal

Yoon Ha Chan

Shereef Elmetwaly


Other Participants

Neocles Leontis, Bowling Green University

Evgeny Nudler, NYU medical school

Jason Wang, New Jersey Institute of Technology


Resulting Publications


1. Y. Xin, C. Laing, N. B. Leontis, and T. Schlick. Annotation of tertiary interactions in RNA structures reveals variations and correlations. RNA; 14:2465-2477 (2008).



RNA tertiary motifs play an important role in RNA folding and biochemical functions. To help interpret the complex organization of RNA tertiary interactions, we comprehensively analyze a dataset of 54 high-resolution RNA crystal structures for motif occurrence and correlations. Specifically, we search seven recognized categories of RNA tertiary motifs (coaxial helix, A-minor, ribose zipper, pseudoknot, kissing hairpin, tRNA D-loop/T-loop and tetraloop-tetraloop receptor) by various computer programs. For the non-redundant RNA dataset, we find 615 RNA tertiary interactions (Fig. 1a), most of which occur in the 16S and 23S rRNAs. An exhaustive analysis of these motifs reveals the diversity and variety of A-minor motif interactions and various possible loop-loop receptor interactions that expand upon the tetraloop-tetraloop receptor. Correlations between motifs, such as pseudoknot or coaxial helix with A-minor, reveal higher-order patterns (Fig. 1b). These findings may help define tertiary structure restraints for RNA tertiary structure prediction. A complete annotation of the RNA diagrams for our dataset are available at



Figure 1 (a) The distribution of RNA tertiary motifs in the non-redundant dataset of 54 high-resolution crystal structures. (b) Annotated diagram of the TPP riboswitch (PDB: 2GDI) shows several correlated motifs.



2. C. Laing, and T. Schlick. Analysis of four-way junctions in RNA structures. JMB; doi:10.1016/j.jmb.2009.04.084; May 13, (2009).



RNA secondary structures can be divided into helical regions composed of canonical Watson-Crick and related basepairs, as well as single-stranded regions such as hairpin loops, internal loops, and junctions. These elements function as building blocks in the design of diverse RNA molecules with various fundamental functions in the cell. To better understand the intricate architecture of three-dimensional RNAs, we analyze existing RNA 4-way junctions in terms of basepair interactions and three-dimensional configurations. Specifically, we identify nine broad junction families according to coaxial stacking patterns and helical configurations (Fig. 2a). We find that helices within junctions tend to arrange in roughly parallel and perpendicular patterns, and stabilize their conformations using common tertiary motifs like coaxial stacking, loop-helix interaction, and helix packing interaction (Fig. 2b). Our analysis also reveals a number of highly conserved basepair interaction patterns and novel tertiary motifs such as A-minor-coaxial stacking combinations and sarcin/ricin motif variants. Such analyses of RNA building blocks can ultimately help in the difficult task of RNA 3D structure prediction.


Figure 2 a) Classification of RNA four-way junctions into nine families according to their coaxial stacking properties and flexible helical arms. b) Diagram of a four-way junction composed of two coaxial helices arranged in a perpendicular fashion. The conformation is stabilized by key 3D motifs.



3. T. Schlick. Mathematical and Biological Scientists Assess the State-of-the-Art in RNA Science at an IMA Workshop ‘RNA in Biology, Bioengineering and Biotechnology’, Intl. J. Mult. Sci. Eng., In Press (2009).



Highlights of the IMA workshop RNA in Biology, Bioengineering, and Biotechnology are summarized, including recent developments in RNA secondary structure prediction and RNA design, innovative mathematical constructs for RNA structure, bioinformatics advances in RNA structure analysis and prediction, and experimental progress in RNA folding and imaging.



Related links

A complete annotation of the RNA diagrams for our dataset is available at: