Annotation of tertiary interactions in RNA structures reveals variations and correlations.

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 data set 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 nonredundant RNA data set, we find 613 RNA tertiary interactions, most of which occur in the 16S and 23S rRNAs. An analysis of these motifs reveals the diversity and variety of A-minor motif interactions and the 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. These findings may ultimately help define tertiary structure restraints for RNA tertiary structure prediction. A complete annotation of the RNA diagrams for our data set is available at http://www.biomath.nyu.edu/motifs/.

[1]  N. Seeman,et al.  The general structure of transfer RNA molecules. , 1974, Proceedings of the National Academy of Sciences of the United States of America.

[2]  J L Sussman,et al.  Crystal structure of yeast phenylalanine transfer RNA. II. Structural features and functional implications. , 1978, Journal of molecular biology.

[3]  J L Sussman,et al.  Crystal structure of yeast phenylalanine transfer RNA. I. Crystallographic refinement. , 1978, Journal of molecular biology.

[4]  A Masoni,et al.  [A new principle]. , 1980, Giornale italiano di cardiologia.

[5]  C. Pleij,et al.  A new principle of RNA folding based on pseudoknotting. , 1985, Nucleic acids research.

[6]  A. R. Srinivasan,et al.  The nucleic acid database. A comprehensive relational database of three-dimensional structures of nucleic acids. , 1992, Biophysical journal.

[7]  U. Hobohm,et al.  Selection of representative protein data sets , 1992, Protein science : a publication of the Protein Society.

[8]  I. Tinoco,et al.  Characterization of a "kissing" hairpin complex derived from the human immunodeficiency virus genome. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[9]  S C Harvey,et al.  A quantitative model of the Escherichia coli 16 S RNA in the 30 S ribosomal subunit. , 1994, Journal of molecular biology.

[10]  F. Michel,et al.  Frequent use of the same tertiary motif by self‐folding RNAs. , 1995, The EMBO journal.

[11]  N. Seeman,et al.  A nomenclature of junctions and branchpoints in nucleic acids. , 1995, Nucleic acids research.

[12]  C. Kundrot,et al.  Crystal Structure of a Group I Ribozyme Domain: Principles of RNA Packing , 1996, Science.

[13]  A. Pyle,et al.  Remarkable morphological variability of a common RNA folding motif: the GNRA tetraloop-receptor interaction. , 1997, Journal of molecular biology.

[14]  E. Westhof,et al.  Hierarchy and dynamics of RNA folding. , 1997, Annual review of biophysics and biomolecular structure.

[15]  C Massire,et al.  MANIP: an interactive tool for modelling RNA. , 1998, Journal of molecular graphics & modelling.

[16]  D. Patel,et al.  Stitching together RNA tertiary architectures. , 1999, Journal of molecular biology.

[17]  P. Moore,et al.  Structural motifs in RNA. , 1999, Annual review of biochemistry.

[18]  Batey,et al.  Tertiary Motifs in RNA Structure and Folding. , 1999, Angewandte Chemie.

[19]  T. Steitz,et al.  The complete atomic structure of the large ribosomal subunit at 2.4 A resolution. , 2000, Science.

[20]  J. Ng,et al.  PseudoBase: a database with RNA pseudoknots , 2000, Nucleic Acids Res..

[21]  B. Felden,et al.  Emerging views on tmRNA‐mediated protein tagging and ribosome rescue , 2001, Molecular microbiology.

[22]  Thomas A. Steitz,et al.  RNA tertiary interactions in the large ribosomal subunit: The A-minor motif , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[23]  E. Westhof,et al.  Geometric nomenclature and classification of RNA base pairs. , 2001, RNA.

[24]  G. Ruvkun Molecular biology. Glimpses of a tiny RNA world. , 2001, Science.

[25]  A. Rich,et al.  Metal ions and flexibility in a viral RNA pseudoknot at atomic resolution , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[26]  Scott M Stagg,et al.  Modeling a minimal ribosome based on comparative sequence analysis. , 2002, Journal of molecular biology.

[27]  Steven E. Brenner,et al.  SCOR: a Structural Classification of RNA database , 2002, Nucleic Acids Res..

[28]  Gregory J. Hannon,et al.  Insight Review Articles , 2022 .

[29]  Makio Tamura,et al.  Sequence and structural conservation in RNA ribose zippers. , 2002, Journal of molecular biology.

[30]  J. Doudna,et al.  Specificity of RNA–RNA helix recognition , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[31]  G. Fox,et al.  Frequent occurrence of the T-loop RNA folding motif in ribosomal RNAs. , 2002, RNA.

[32]  Eric Westhof,et al.  The non-Watson-Crick base pairs and their associated isostericity matrices. , 2002, Nucleic acids research.

[33]  S. Gottesman,et al.  A small RNA regulates the expression of genes involved in iron metabolism in Escherichia coli , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[34]  John D. Westbrook,et al.  Tools for the automatic identification and classification of RNA base pairs , 2003, Nucleic Acids Res..

[35]  W. Olson,et al.  3DNA: a software package for the analysis, rebuilding and visualization of three-dimensional nucleic acid structures. , 2003, Nucleic acids research.

[36]  T. Steitz,et al.  The roles of ribosomal proteins in the structure assembly, and evolution of the large ribosomal subunit. , 2004, Journal of molecular biology.

[37]  H. Hansma,et al.  Building Programmable Jigsaw Puzzles with RNA , 2004, Science.

[38]  S. Brenner,et al.  RNA structural motifs: building blocks of a modular biomolecule , 2005, Quarterly Reviews of Biophysics.

[39]  D. P. Aalberts,et al.  Asymmetry in RNA pseudoknots: observation and theory , 2005, Nucleic acids research.

[40]  E. Westhof,et al.  The interaction networks of structured RNAs. , 2006, Nucleic acids research.

[41]  E Westhof,et al.  The A-minor motifs in the decoding recognition process. , 2006, Biochimie.

[42]  E. Westhof,et al.  Topology of three-way junctions in folded RNAs. , 2006, RNA.

[43]  N. Leontis,et al.  Controlling RNA self-assembly to form filaments , 2006, Nucleic acids research.

[44]  E. Westhof,et al.  The building blocks and motifs of RNA architecture. , 2006, Current opinion in structural biology.

[45]  L. Jaeger,et al.  The architectonics of programmable RNA and DNA nanostructures. , 2006, Current opinion in structural biology.

[46]  Sylvie Hamel,et al.  Modeling RNA tertiary structure motifs by graph-grammars , 2007, Nucleic acids research.

[47]  William Stafford Noble,et al.  Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project , 2007, Nature.

[48]  J. Steitz,et al.  Switching from Repression to Activation: MicroRNAs Can Up-Regulate Translation , 2007, Science.

[49]  D. Baker,et al.  Automated de novo prediction of native-like RNA tertiary structures , 2007, Proceedings of the National Academy of Sciences.

[50]  Tao Pan,et al.  Folding of noncoding RNAs during transcription facilitated by pausing-induced nonnative structures , 2007, Proceedings of the National Academy of Sciences.

[51]  J. Maizel,et al.  RNA2D3D: A program for Generating, Viewing, and Comparing 3-Dimensional Models of RNA , 2008, Journal of biomolecular structure & dynamics.

[52]  Craig L. Zirbel,et al.  FR3D: finding local and composite recurrent structural motifs in RNA 3D structures , 2007, Journal of mathematical biology.

[53]  Cody W. Geary,et al.  Comprehensive features of natural and in vitro selected GNRA tetraloop-binding receptors , 2007, Nucleic acids research.

[54]  F. Major,et al.  The MC-Fold and MC-Sym pipeline infers RNA structure from sequence data , 2008, Nature.

[55]  Jesse Stombaugh,et al.  RNA 3D Structural Motifs: Definition, Identification, Annotation, and Database Searching , 2009 .

[56]  Michael Sarver,et al.  FR 3 D : finding local and composite recurrent structural motifs in RNA 3 D structures , 2010 .