Finding 3D motifs in ribosomal RNA structures

The identification of small structural motifs and their organization into larger subassemblies is of fundamental interest in the analysis, prediction and design of 3D structures of large RNAs. This problem has been studied only sparsely, as most of the existing work is limited to the characterization and discovery of motifs in RNA secondary structures. We present a novel geometric method for the characterization and identification of structural motifs in 3D rRNA molecules. This method enables the efficient recognition of known 3D motifs, such as tetraloops, E-loops, kink-turns and others. Furthermore, it provides a new way of characterizing complex 3D motifs, notably junctions, that have been defined and identified in the secondary structure but have not been analyzed and classified in three dimensions. We demonstrate the relevance and utility of our approach by applying it to the Haloarcula marismortui large ribosomal unit. Pending the implementation of a dedicated web server, the code accompanying this article, written in JAVA, is available upon request from the contact author.

[1]  Ali Mokdad,et al.  Ribostral: an RNA 3D alignment analyzer and viewer based on basepair isostericities , 2006, Bioinform..

[2]  E. Westhof,et al.  Analysis of RNA motifs. , 2003, Current opinion in structural biology.

[3]  Anna Marie Pyle,et al.  RNA structure comparison, motif search and discovery using a reduced representation of RNA conformational space. , 2003, Nucleic acids research.

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

[5]  A. Pardi,et al.  Solution structure of the CUUG hairpin loop: a novel RNA tetraloop motif. , 1995, Biochemistry.

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

[7]  E. Westhof,et al.  A common motif organizes the structure of multi-helix loops in 16 S and 23 S ribosomal RNAs. , 1998, Journal of molecular biology.

[8]  J. M. Diamond,et al.  Thermodynamics of three-way multibranch loops in RNA. , 2001, Biochemistry.

[9]  T. Steitz,et al.  The kink‐turn: a new RNA secondary structure motif , 2001, The EMBO journal.

[10]  Hung-Chung Huang,et al.  The application of cluster analysis in the intercomparison of loop structures in RNA. , 2005, RNA.

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

[12]  A. Tannenbaum,et al.  Single nucleotide RNA choreography , 2006, Nucleic acids research.

[13]  Eckart Bindewald,et al.  RNAJunction: a database of RNA junctions and kissing loops for three-dimensional structural analysis and nanodesign , 2007, Nucleic Acids Res..

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

[15]  Peter Willett,et al.  Representation, searching and discovery of patterns of bases in complex RNA structures , 2003, J. Comput. Aided Mol. Des..

[16]  Ruth Nussinov,et al.  ARTS: alignment of RNA tertiary structures , 2005, ECCB/JBI.

[17]  Anna Marie Pyle,et al.  The identification of novel RNA structural motifs using COMPADRES: an automated approach to structural discovery. , 2004, Nucleic acids research.

[18]  D. Turner,et al.  Experimentally derived nearest-neighbor parameters for the stability of RNA three- and four-way multibranch loops. , 2002, Biochemistry.

[19]  K. Swinger,et al.  Common and distinctive features of GNRA tetraloops based on a GUAA tetraloop structure at 1.4 A resolution. , 2003, RNA.

[20]  Steven E. Brenner,et al.  SCOR: Structural Classification of RNA, version 2.0 , 2004, Nucleic Acids Res..

[21]  Peter Clote,et al.  DIAL: a web server for the pairwise alignment of two RNA three-dimensional structures using nucleotide, dihedral angle and base-pairing similarities , 2007, Nucleic Acids Res..

[22]  Bernard Chazelle,et al.  Shape distributions , 2002, TOGS.

[23]  A. Serganov,et al.  The crystal structure of UUCG tetraloop. , 2000, Journal of molecular biology.

[24]  Jan Gorodkin,et al.  The foldalign web server for pairwise structural RNA alignment and mutual motif search , 2005, Nucleic Acids Res..

[25]  T. Huynh-Dinh,et al.  Comparison between CUUG and UUCG tetraloops: thermodynamic stability and structural features analyzed by UV absorption and vibrational spectroscopy. , 2001, Nucleic acids research.

[26]  Bin Tian,et al.  RADAR: a web server for RNA data analysis and research , 2007, Nucleic Acids Res..

[27]  François Major,et al.  Automated extraction and classification of RNA tertiary structure cyclic motifs , 2006, Nucleic acids research.

[28]  D C Richardson,et al.  RNA backbone rotamers--finding your way in seven dimensions. , 2005, Biochemical Society transactions.

[29]  Emmanuel Tannenbaum,et al.  Automated identification of RNA conformational motifs: theory and application to the HM LSU 23S rRNA. , 2003, Nucleic acids research.

[30]  E Westhof,et al.  Involvement of a GNRA tetraloop in long-range RNA tertiary interactions. , 1994, Journal of molecular biology.

[31]  I. Tinoco,et al.  How RNA folds. , 1999, Journal of molecular biology.

[32]  D. Patel,et al.  Base dynamics in a UUCG tetraloop RNA hairpin characterized by 15N spin relaxation: correlations with structure and stability. , 1997, RNA.

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

[34]  Ruth Nussinov,et al.  The ARTS web server for aligning RNA tertiary structures , 2006, Nucleic Acids Res..

[35]  Nan Yu,et al.  The Comparative RNA Web (CRW) Site: an online database of comparative sequence and structure information for ribosomal, intron, and other RNAs , 2002, BMC Bioinformatics.

[36]  T. Steitz,et al.  2SB5 The complete atomic structure of the large ribosomal subunit from Haloarcula marismortui , 2000 .

[37]  P. Gendron,et al.  Quantitative analysis of nucleic acid three-dimensional structures. , 2001, Journal of molecular biology.