Statistical analysis of RNA backbone

Local conformation is an important determinant of RNA catalysis and binding. The analysis of RNA conformation is particularly difficult due to the large number of degrees of freedom (torsion angles) per residue. Proteins, by comparison, have many fewer degrees of freedom per residue. In this work, we use and extend classical tools from statistics and signal processing to search for clusters in RNA conformational space. Results are reported both for scalar analysis, where each torsion angle is separately studied, and for vectorial analysis, where several angles are simultaneously clustered. Adapting techniques from vector quantization and clustering to the RNA structure, we find torsion angle clusters and RNA conformational motifs. We validate the technique using well-known conformational motifs, showing that the simultaneous study of the total torsion angle space leads to results consistent with known motifs reported in the literature and also to the finding of new ones

[1]  P. Gendron,et al.  NMR structure of the active conformation of the Varkud satellite ribozyme cleavage site , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[2]  N. Wingreen,et al.  Flexibility of α-Helices: Results of a Statistical Analysis of Database Protein Structures , 2003 .

[3]  Ned S Wingreen,et al.  Flexibility of alpha-helices: results of a statistical analysis of database protein structures. , 2002, Journal of molecular biology.

[4]  A. Pardi,et al.  GNRA tetraloops make a U-turn. , 1995, RNA.

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

[6]  G. Rose,et al.  A complete conformational map for RNA. , 1999, Journal of molecular biology.

[7]  C R Woese,et al.  Architecture of ribosomal RNA: constraints on the sequence of "tetra-loops". , 1990, Proceedings of the National Academy of Sciences of the United States of America.

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

[9]  J. Tenenbaum,et al.  A global geometric framework for nonlinear dimensionality reduction. , 2000, Science.

[10]  W. Olson,et al.  Configurational statistics of polynucleotide chains. A single virtual bond treatment. , 1975, Macromolecules.

[11]  M. Sundaralingam,et al.  Stereochemistry of nucleic acids and their constituents. XIX. Copper binding sites and mechanism of G-C selective denaturation of DNA. Crystal and molecular structures of guanine-copper(II) chloride and cytosine-copper(II) chloride complexes. , 1971, Journal of molecular biology.

[12]  Wolfram Saenger,et al.  Principles of Nucleic Acid Structure , 1983 .

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

[14]  G. N. Ramachandran,et al.  Stereochemistry of polypeptide chain configurations. , 1963, Journal of molecular biology.

[15]  W. B. Arendall,et al.  RNA backbone is rotameric , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[16]  Thomas M. Cover,et al.  Elements of Information Theory , 2005 .

[17]  Helen M Berman,et al.  RNA conformational classes. , 2004, Nucleic acids research.

[18]  Michael I. Jordan,et al.  On Spectral Clustering: Analysis and an algorithm , 2001, NIPS.

[19]  J. Feigon,et al.  Solution structure of a GAAA tetraloop receptor RNA , 1997, The EMBO journal.

[20]  R. Langridge.  Nucleic acids and polynucleotides , 1969, Journal of cellular physiology.

[21]  G. N. Ramachandran,et al.  Conformation of polypeptides and proteins. , 1968, Advances in protein chemistry.

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

[23]  Robert M. Gray,et al.  An Algorithm for Vector Quantizer Design , 1980, IEEE Trans. Commun..

[24]  Sidney M. Hecht,et al.  Bioorganic chemistry : nucleic acids , 1996 .

[25]  T. Cech.  Ribozymes, the first 20 years. , 2001, Biochemical Society transactions.

[26]  R. Gray,et al.  Vector quantization , 1984, IEEE ASSP Magazine.

[27]  E. Westhof,et al.  Modelling of the three-dimensional architecture of group I catalytic introns based on comparative sequence analysis. , 1990, Journal of molecular biology.

[28]  A. Pyle,et al.  Stepping through an RNA structure: A novel approach to conformational analysis. , 1998, Journal of molecular biology.

[29]  M Sundaralingam,et al.  Stereochemistry of nucleic acids and their constituents. IX. The conformation of the antibiotic puromycin dihydrochloride pentahydrate. , 1969, Proceedings of the National Academy of Sciences of the United States of America.

[30]  G. Rose,et al.  RNABase: an annotated database of RNA structures , 2003, Nucleic Acids Res..

[31]  A. Hinneburg,et al.  Database support for 3D-protein data set analysis , 2003, 15th International Conference on Scientific and Statistical Database Management, 2003..

[32]  Allen Gersho,et al.  Vector quantization and signal compression , 1991, The Kluwer international series in engineering and computer science.

[33]  M. Sundaralingam,et al.  Stereochemistry of nucleic acids and their constituents. IV. Allowed and preferred conformations of nucleosides, nucleoside mono‐, di‐, tri‐, tetraphosphates, nucleic acids and polynucleotides , 1969 .

[34]  W. Scott.  Ribozymes , 1998, Current Biology.