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).
Summary
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 http://www.biomath.nyu.edu/motifs/.
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).
Summary
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 ÔRNA in Biology, Bioengineering and BiotechnologyÕ, Intl. J. Mult. Sci. Eng., In Press (2009).
Summary
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: