Using an RNA secondary structure partition function to determine confidence in base pairs predicted by free energy minimization.

A partition function calculation for RNA secondary structure is presented that uses a current set of nearest neighbor parameters for conformational free energy at 37 degrees C, including coaxial stacking. For a diverse database of RNA sequences, base pairs in the predicted minimum free energy structure that are predicted by the partition function to have high base pairing probability have a significantly higher positive predictive value for known base pairs. For example, the average positive predictive value, 65.8%, is increased to 91.0% when only base pairs with probability of 0.99 or above are considered. The quality of base pair predictions can also be increased by the addition of experimentally determined constraints, including enzymatic cleavage, flavin mono-nucleotide cleavage, and chemical modification. Predicted secondary structures can be color annotated to demonstrate pairs with high probability that are therefore well determined as compared to base pairs with lower probability of pairing.

[1]  M. Sundaralingam,et al.  Structlre of transfer RNA molecules containing the long variable loop. , 1976, Nucleic acids research.

[2]  Peter Walter,et al.  Signal recognition particle contains a 7S RNA essential for protein translocation across the endoplasmic reticulum , 1982, Nature.

[3]  M. Speek,et al.  Structural analyses of E. coli 5S RNA fragments, their associates and complexes with proteins L18 and L25. , 1982, Nucleic acids research.

[4]  K Miura,et al.  Chemical modification of guanine residues of mouse 5 S ribosomal RNA with kethoxal. (Nucleosides and nucleotides 46). , 1983, Biochimica et biophysica acta.

[5]  D. Draper,et al.  Secondary structure of a 345-base RNA fragment covering the S8/S15 protein binding domain of Escherichia coli 16S ribosomal RNA. , 1985, Biochemistry.

[6]  H. Noller,et al.  Rapid chemical probing of conformation in 16 S ribosomal RNA and 30 S ribosomal subunits using primer extension. , 1986, Journal of molecular biology.

[7]  D. Mccormick.  Sequence the Human Genome , 1986, Bio/Technology.

[8]  R. Garrett,et al.  Structure and accessibility of domain I of Escherichia coli 23 S RNA in free RNA, in the L24-RNA complex and in 50 S subunits. Implications for ribosomal assembly. , 1987, Journal of molecular biology.

[9]  J. Ebel,et al.  Probing the structure of RNAs in solution. , 1987, Nucleic acids research.

[10]  G. Knapp.  Enzymatic approaches to probing of RNA secondary and tertiary structure. , 1989, Methods in enzymology.

[11]  M. Zuker.  On finding all suboptimal foldings of an RNA molecule. , 1989, Science.

[12]  K. Umesono,et al.  Comparative and functional anatomy of group II catalytic introns--a review. , 1989, Gene.

[13]  L. Grivell,et al.  Structural analysis of a group II intron by chemical modifications and minimal energy calculations. , 1990, Journal of Biomolecular Structure and Dynamics.

[14]  J. McCaskill.  The equilibrium partition function and base pair binding probabilities for RNA secondary structure , 1990, Biopolymers.

[15]  S. Gerbi,et al.  Changes in 7SL RNA conformation during the signal recognition particle cycle. , 1991, The EMBO journal.

[16]  K. Pleij,et al.  A conserved pseudoknot in telomerase RNA. , 1991, Nucleic acids research.

[17]  M. Ares,et al.  Efficient association of U2 snRNPs with pre-mRNA requires an essential U2 RNA structural element. , 1991, Genes & development.

[18]  Daniel P. Romero,et al.  A conserved secondary structure for telomerase RNA , 1991, Cell.

[19]  Christian Zwieb,et al.  The signal recognition particle database (SRPDB) , 1993, Nucleic Acids Res..

[20]  Carl R. Woese,et al.  4 Probing RNA Structure, Function, and History by Comparative Analysis , 1993 .

[21]  Sergey Steinberg,et al.  Compilation of tRNA sequences and sequences of tRNA genes , 2004, Nucleic Acids Res..

[22]  Walter Fontana,et al.  Fast folding and comparison of RNA secondary structures , 1994 .

[23]  A. Tranguch,et al.  Structure-sensitive RNA footprinting of yeast nuclear ribonuclease P. , 1994, Biochemistry.

[24]  A. E. Walter,et al.  Coaxial stacking of helixes enhances binding of oligoribonucleotides and improves predictions of RNA folding. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[25]  A. E. Walter,et al.  The stability and structure of tandem GA mismatches in RNA depend on closing base pairs. , 1994, Biochemistry.

[26]  N. Pace,et al.  Phylogenetic comparative chemical footprint analysis of the interaction between ribonuclease P RNA and tRNA. , 1994, The EMBO journal.

[27]  M. Zuker,et al.  "Well-determined" regions in RNA secondary structure prediction: analysis of small subunit ribosomal RNA. , 1995, Nucleic acids research.

[28]  T. Cech,et al.  Analysis of the structure of Tetrahymena nuclear RNAs in vivo: telomerase RNA, the self-splicing rRNA intron, and U2 snRNA. , 1995, RNA.

[29]  E Westhof,et al.  An interactive framework for RNA secondary structure prediction with a dynamical treatment of constraints. , 1995, Journal of molecular biology.

[30]  B. Barrell,et al.  Life with 6000 Genes , 1996, Science.

[31]  A. E. Walter,et al.  Thermodynamics of coaxially stacked helixes with GA and CC mismatches. , 1996, Biochemistry.

[32]  M. Huynen,et al.  Assessing the reliability of RNA folding using statistical mechanics. , 1997, Journal of molecular biology.

[33]  D. Turner,et al.  Secondary structure model of the RNA recognized by the reverse transcriptase from the R2 retrotransposable element. , 1997, RNA.

[34]  Detlev Riesner,et al.  Viroid processing: switch from cleavage to ligation is driven by a change from a tetraloop to a loop E conformation , 1997, The EMBO journal.

[35]  P. Burgstaller,et al.  Flavin-Dependent Photocleavage of RNA at G·U Base Pairs , 1997 .

[36]  E Westhof,et al.  Isoalloxazine derivatives promote photocleavage of natural RNAs at G.U base pairs embedded within helices. , 1997, Nucleic acids research.

[37]  J. Berg.  Genome sequence of the nematode C. elegans: a platform for investigating biology. , 1998, Science.

[38]  Andrew Smith.  Genome sequence of the nematode C-elegans: A platform for investigating biology , 1998 .

[39]  James W. Brown.  The ribonuclease P database , 1998, Nucleic Acids Res..

[40]  F. Michel,et al.  Differential chemical probing of a group II self-splicing intron identifies bases involved in tertiary interactions and supports an alternative secondary structure model of domain V. , 1998, RNA.

[41]  P. Borer,et al.  Three-dimensional folding of an RNA hairpin required for packaging HIV-1. , 1998, Journal of molecular biology.

[42]  T. Pan,et al.  Interaction of structural modules in substrate binding by the ribozyme from Bacillus subtilis RNase P. , 1998, Nucleic acids research.

[43]  M. Zuker,et al.  Using reliability information to annotate RNA secondary structures. , 1998, RNA.

[44]  D. Turner,et al.  Thermodynamic parameters for an expanded nearest-neighbor model for formation of RNA duplexes with Watson-Crick base pairs. , 1998, Biochemistry.

[45]  E Rivas,et al.  A dynamic programming algorithm for RNA structure prediction including pseudoknots. , 1998, Journal of molecular biology.

[46]  James W. Brown,et al.  The Ribonuclease P Database , 1994, Nucleic Acids Res..

[47]  Christian N. S. Pedersen,et al.  Fast evaluation of internal loops in RNA secondary structure prediction , 1999, Bioinform..

[48]  J. Sabina,et al.  Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structure. , 1999, Journal of molecular biology.

[49]  D. Turner,et al.  Predicting oligonucleotide affinity to nucleic acid targets. , 1999, RNA.

[50]  Christian Zwieb,et al.  The Signal Recognition Particle Database (SRPDB) , 1993, Nucleic Acids Res..

[51]  P. Schuster,et al.  Complete suboptimal folding of RNA and the stability of secondary structures. , 1999, Biopolymers.

[52]  F. Schluenzen,et al.  Structure of Functionally Activated Small Ribosomal Subunit , 2000 .

[53]  The Arabidopsis Genome Initiative.  Analysis of the genome sequence of the flowering plant Arabidopsis thaliana , 2000, Nature.

[54]  Miroslawa Z. Barciszewska,et al.  5S ribosomal RNA database Y2K , 2000, Nucleic Acids Res..

[55]  Stephen M. Mount,et al.  The genome sequence of Drosophila melanogaster. , 2000, Science.

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

[57]  Christian Zwieb,et al.  SRPDB (Signal Recognition Particle Database) , 2000, Nucleic Acids Res..

[58]  Jonathan A. Eisen,et al.  Microbial genome sequencing , 2000, Nature.

[59]  F. Schluenzen,et al.  Structure of Functionally Activated Small Ribosomal Subunit at 3.3 Å Resolution , 2000, Cell.

[60]  T. Steitz,et al.  The structural basis of ribosome activity in peptide bond synthesis. , 2000, Science.

[61]  C. Vonrhein,et al.  Structure of the 30S ribosomal subunit , 2000, Nature.

[62]  Peter F. Stadler,et al.  Prediction of RNA Base Pairing Probabilities on Massively Parallel Computers , 2000, J. Comput. Biol..

[63]  D. Bartel,et al.  One sequence, two ribozymes: implications for the emergence of new ribozyme folds. , 2000, Science.

[64]  H. Heus,et al.  Structure of the ribozyme substrate hairpin of Neurospora VS RNA: a close look at the cleavage site. , 2000, RNA.

[65]  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.

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

[67]  S. Eddy.  Non–coding RNA genes and the modern RNA world , 2001, Nature Reviews Genetics.

[68]  P. Stadler,et al.  Design of multistable RNA molecules. , 2001, RNA.

[69]  D. Turner,et al.  2 – Thermodynamics of RNA Secondary Structure Formation , 2001 .

[70]  L. Lim,et al.  An Abundant Class of Tiny RNAs with Probable Regulatory Roles in Caenorhabditis elegans , 2001, Science.

[71]  T. Tuschl,et al.  Identification of Novel Genes Coding for Small Expressed RNAs , 2001, Science.

[72]  C. Lawrence,et al.  Statistical prediction of single-stranded regions in RNA secondary structure and application to predicting effective antisense target sites and beyond. , 2001, Nucleic acids research.

[73]  J. V. Moran,et al.  Initial sequencing and analysis of the human genome. , 2001, Nature.

[74]  R. Gutell,et al.  The accuracy of ribosomal RNA comparative structure models. , 2002, Current opinion in structural biology.

[75]  Thomas A Steitz,et al.  Structural insights into peptide bond formation , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[76]  Jennifer A. Doudna,et al.  The chemical repertoire of natural ribozymes , 2002, Nature.

[77]  D. Turner,et al.  Dynalign: an algorithm for finding the secondary structure common to two RNA sequences. , 2002, Journal of molecular biology.

[78]  Colin N. Dewey,et al.  Initial sequencing and comparative analysis of the mouse genome. , 2002 .

[79]  K. Weeks,et al.  Differential helix stabilities and sites pre-organized for tertiary interactions revealed by monitoring local nucleotide flexibility in the bI5 group I intron RNA. , 2003, Biochemistry.

[80]  Niles A. Pierce,et al.  A partition function algorithm for nucleic acid secondary structure including pseudoknots , 2003, J. Comput. Chem..

[81]  C. Lawrence,et al.  A statistical sampling algorithm for RNA secondary structure prediction. , 2003, Nucleic acids research.

[82]  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.

[83]  A D Tsodikov,et al.  Thermodynamic criteria for high hit rate antisense oligonucleotide design. , 2003, Nucleic acids research.

[84]  Christian Zwieb,et al.  SRPDB: Signal Recognition Particle Database , 2003, Nucleic Acids Res..

[85]  Ivo L. Hofacker,et al.  Vienna RNA secondary structure server , 2003, Nucleic Acids Res..

[86]  Weixiong Zhang,et al.  An Iterated loop matching approach to the prediction of RNA secondary structures with pseudoknots , 2004, Bioinform..

[87]  D. Turner,et al.  Incorporating chemical modification constraints into a dynamic programming algorithm for prediction of RNA secondary structure. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[88]  Mathias Sprinzl,et al.  Compilation of tRNA sequences and sequences of tRNA genes , 1993, Nucleic Acids Res..

[89]  V. Ramakrishnan,et al.  Structure of the 30 S ribosomal subunit , 2022 .