Folding and finding RNA secondary structure.

Optimal exploitation of the expanding database of sequences requires rapid finding and folding of RNAs. Methods are reviewed that automate folding and discovery of RNAs with algorithms that couple thermodynamics with chemical mapping, NMR, and/or sequence comparison. New functional noncoding RNAs in genome sequences can be found by combining sequence comparison with the assumption that functional noncoding RNAs will have more favorable folding free energies than other RNAs. When a new RNA is discovered, experiments and sequence comparison can restrict folding space so that secondary structure can be rapidly determined with the help of predicted free energies. In turn, secondary structure restricts folding in three dimensions, which allows modeling of three-dimensional structure. An example from a domain of a retrotransposon is described. Discovery of new RNAs and their structures will provide insights into evolution, biology, and design of therapeutics. Applications to studies of evolution are also reviewed.

[1]  T. Steitz,et al.  The roles of RNA in the synthesis of protein. , 2011, Cold Spring Harbor perspectives in biology.

[2]  Eric Westhof,et al.  Predicting and modeling RNA architecture. , 2011, Cold Spring Harbor perspectives in biology.

[3]  E. Kierzek.  Binding of short oligonucleotides to RNA: studies of the binding of common RNA structural motifs to isoenergetic microarrays. , 2009, Biochemistry.

[4]  D. Mathews,et al.  Improved RNA secondary structure prediction by maximizing expected pair accuracy. , 2009, RNA.

[5]  Walter N. Moss,et al.  Secondary structures for 5' regions of R2 retrotransposon RNAs reveal a novel conserved pseudoknot and regions that evolve under different constraints. , 2009, Journal of molecular biology.

[6]  Morgan C. Giddings,et al.  Influence of nucleotide identity on ribose 2'-hydroxyl reactivity in RNA. , 2009, RNA.

[7]  D. Mathews,et al.  Stochastic sampling of the RNA structural alignment space , 2009, Nucleic acids research.

[8]  Kiyoshi Asai,et al.  Prediction of RNA secondary structure using generalized centroid estimators , 2009, Bioinform..

[9]  Kristin Reiche,et al.  Structural profiles of human miRNA families from pairwise clustering , 2009, Bioinform..

[10]  D. Mathews,et al.  Accurate SHAPE-directed RNA structure determination , 2009, Proceedings of the National Academy of Sciences.

[11]  Sebastian Will,et al.  RNAalifold: improved consensus structure prediction for RNA alignments , 2008, BMC Bioinformatics.

[12]  D. Les,et al.  Phylogenetic analysis of the internal transcribed spacer (ITS) region in Menyanthaceae using predicted secondary structure. , 2008, Molecular phylogenetics and evolution.

[13]  Q. Cui,et al.  An Analysis of Human MicroRNA and Disease Associations , 2008, PloS one.

[14]  David H. Mathews,et al.  NMR-Assisted Prediction of RNA Secondary Structure: Identification of a Probable Pseudoknot in the Coding Region of an R2 Retrotransposon , 2008, Journal of the American Chemical Society.

[15]  Chuan-Sheng Foo,et al.  A max-margin model for efficient simultaneous alignment and folding of RNA sequences , 2008, ISMB.

[16]  C. Feschotte.  Transposable elements and the evolution of regulatory networks , 2008, Nature Reviews Genetics.

[17]  Vegeir Knudsen,et al.  NOBAI: a web server for character coding of geometrical and statistical features in RNA structure , 2008, Nucleic Acids Res..

[18]  Stefan L Ameres,et al.  The impact of target site accessibility on the design of effective siRNAs , 2008, Nature Biotechnology.

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

[20]  K. Morris,et al.  RNA and transcriptional modulation of gene expression , 2008, Cell cycle.

[21]  D. Mathews,et al.  PARTS: Probabilistic Alignment for RNA joinT Secondary structure prediction , 2008, Nucleic acids research.

[22]  D. Turner,et al.  Isoenergetic penta- and hexanucleotide microarray probing and chemical mapping provide a secondary structure model for an RNA element orchestrating R2 retrotransposon protein function , 2008, Nucleic acids research.

[23]  David H. Mathews,et al.  Efficient siRNA selection using hybridization thermodynamics , 2007, Nucleic acids research.

[24]  Tobias Müller,et al.  The ITS2 Database II: homology modelling RNA structure for molecular systematics , 2007, Nucleic Acids Res..

[25]  Matthew D Disney,et al.  A small molecule microarray platform to select RNA internal loop-ligand interactions. , 2007, ACS chemical biology.

[26]  Chi Yu Chan,et al.  Effect of target secondary structure on RNAi efficiency. , 2007, RNA.

[27]  Kevin P. Murphy,et al.  Efficient parameter estimation for RNA secondary structure prediction , 2007, ISMB/ECCB.

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

[29]  I. K. Jordan,et al.  Origin and Evolution of Human microRNAs From Transposable Elements , 2007, Genetics.

[30]  Jessica L. Childs-Disney,et al.  Using Selection to Identify and Chemical Microarray to Study the RNA Internal Loops Recognized by 6′‐N‐Acylated Kanamycin A , 2007, Chembiochem : a European journal of chemical biology.

[31]  Dang D. Long,et al.  Potent effect of target structure on microRNA function , 2007, Nature Structural &Molecular Biology.

[32]  K. Weeks,et al.  A fast-acting reagent for accurate analysis of RNA secondary and tertiary structure by SHAPE chemistry. , 2007, Journal of the American Chemical Society.

[33]  Jan Gorodkin,et al.  Multiple structural alignment and clustering of RNA sequences , 2007, Bioinform..

[34]  Rolf Backofen,et al.  Inferring Noncoding RNA Families and Classes by Means of Genome-Scale Structure-Based Clustering , 2007, PLoS Comput. Biol..

[35]  Kiyoshi Asai,et al.  Robust prediction of consensus secondary structures using averaged base pairing probability matrices , 2007, Bioinform..

[36]  Gustavo Caetano-Anollés,et al.  Common evolutionary trends for SINE RNA structures. , 2007, Trends in genetics : TIG.

[37]  G. Caetano-Anollés,et al.  The Origin and Evolution of tRNA Inferred from Phylogenetic Analysis of Structure , 2007, Journal of Molecular Evolution.

[38]  Marcel Turcotte,et al.  Can Clustal-style progressive pairwise alignment of multiple sequences be used in RNA secondary structure prediction? , 2007, BMC Bioinformatics.

[39]  Gaurav Sharma,et al.  Efficient pairwise RNA structure prediction using probabilistic alignment constraints in Dynalign , 2007, BMC Bioinformatics.

[40]  T. Eickbush,et al.  RNA from the 5′ end of the R2 retrotransposon controls R2 protein binding to and cleavage of its DNA target site , 2006, Proceedings of the National Academy of Sciences.

[41]  Xiaoyu Zhang,et al.  Two-Step Recruitment of RNA-Directed DNA Methylation to Tandem Repeats , 2006, PLoS biology.

[42]  Sean R. Eddy,et al.  Efficient pairwise RNA structure prediction and alignment using sequence alignment constraints , 2006, BMC Bioinformatics.

[43]  Serafim Batzoglou,et al.  CONTRAfold: RNA secondary structure prediction without physics-based models , 2006, ISMB.

[44]  J. Gorodkin,et al.  Thousands of corresponding human and mouse genomic regions unalignable in primary sequence contain common RNA structure. , 2006, Genome research.

[45]  Jan Krüger,et al.  RNAhybrid: microRNA target prediction easy, fast and flexible , 2006, Nucleic Acids Res..

[46]  Eugene Berezikov,et al.  Approaches to microRNA discovery , 2006, Nature Genetics.

[47]  Michael Zuker,et al.  22 Predicting RNA Secondary Structure , 2006 .

[48]  David H. Mathews,et al.  Detection of non-coding RNAs on the basis of predicted secondary structure formation free energy change , 2006, BMC Bioinformatics.

[49]  R. Giegerich,et al.  Complete probabilistic analysis of RNA shapes , 2006, BMC Biology.

[50]  D. Turner,et al.  RNA challenges for computational chemists. , 2005, Biochemistry.

[51]  Robert Giegerich,et al.  Consensus shapes: an alternative to the Sankoff algorithm for RNA consensus structure prediction , 2005, Bioinform..

[52]  C. Lawrence,et al.  RNA secondary structure prediction by centroids in a Boltzmann weighted ensemble. , 2005, RNA.

[53]  Gary D. Stormo,et al.  Pairwise local structural alignment of RNA sequences with sequence similarity less than 40% , 2005, Bioinform..

[54]  P. Clote,et al.  Structural RNA has lower folding energy than random RNA of the same dinucleotide frequency. , 2005, RNA.

[55]  K. Gunsalus,et al.  Combinatorial microRNA target predictions , 2005, Nature Genetics.

[56]  Vivek Gowri-Shankar,et al.  Consideration of RNA secondary structure significantly improves likelihood-based estimates of phylogeny: examples from the bilateria. , 2005, Molecular biology and evolution.

[57]  Tobias Müller,et al.  A common core of secondary structure of the internal transcribed spacer 2 (ITS2) throughout the Eukaryota. , 2005, RNA.

[58]  K. Weeks,et al.  RNA structure analysis at single nucleotide resolution by selective 2'-hydroxyl acylation and primer extension (SHAPE). , 2005, Journal of the American Chemical Society.

[59]  Peter F Stadler,et al.  Fast and reliable prediction of noncoding RNAs , 2005, Proc. Natl. Acad. Sci. USA.

[60]  Tobias Müller,et al.  CBCAnalyzer: inferring phylogenies based on compensatory base changes in RNA secondary structures , 2005, Silico Biol..

[61]  Ian Holmes,et al.  Stem Stem Stem Stem Loop Loop Loop LoopLoop Loop Loop Loop Loop Loop Loop , 2005 .

[62]  R. Giegerich,et al.  Fast and effective prediction of microRNA/target duplexes. , 2004, RNA.

[63]  Peter F. Stadler,et al.  Alignment of RNA base pairing probability matrices , 2004, Bioinform..

[64]  D. Mathews.  Using an RNA secondary structure partition function to determine confidence in base pairs predicted by free energy minimization. , 2004, RNA.

[65]  Peter F. Stadler,et al.  The Partition Function Variant of Sankoff's Algorithm , 2004, International Conference on Computational Science.

[66]  Sean R. Eddy,et al.  Evaluation of several lightweight stochastic context-free grammars for RNA secondary structure prediction , 2004, BMC Bioinformatics.

[67]  A. Hatzigeorgiou,et al.  A combined computational-experimental approach predicts human microRNA targets. , 2004, Genes & development.

[68]  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.

[69]  J. Mattick.  RNA regulation: a new genetics? , 2004, Nature Reviews Genetics.

[70]  D. Bartel.  MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[71]  Robert Giegerich,et al.  Abstract shapes of RNA. , 2004, Nucleic acids research.

[72]  Robert Giegerich,et al.  Pure multiple RNA secondary structure alignments: a progressive profile approach , 2004, IEEE/ACM Transactions on Computational Biology and Bioinformatics.

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

[74]  J. Wendel,et al.  Ribosomal ITS sequences and plant phylogenetic inference. , 2003, Molecular phylogenetics and evolution.

[75]  John S Mattick,et al.  Increasing biological complexity is positively correlated with the relative genome-wide expansion of non-protein-coding DNA sequences , 2003, Genome Biology.

[76]  Robert K Jansen,et al.  ITS secondary structure derived from comparative analysis: implications for sequence alignment and phylogeny of the Asteraceae. , 2003, Molecular phylogenetics and evolution.

[77]  Donald H. Burke,et al.  Evolutionary Landscapes for the Acquisition of New Ligand Recognition by RNA Aptamers , 2003, Journal of Molecular Evolution.

[78]  David A Case,et al.  A novel method for finding tRNA genes. , 2003, RNA.

[79]  C. Burge,et al.  The microRNAs of Caenorhabditis elegans. , 2003, Genes & development.

[80]  C. Burge,et al.  Vertebrate MicroRNA Genes , 2003, Science.

[81]  W. Fontana.  Modelling 'evo-devo' with RNA. , 2002, BioEssays : news and reviews in molecular, cellular and developmental biology.

[82]  Peter F. Stadler,et al.  Networks in molecular evolution , 2002 .

[83]  P. Stadler,et al.  Secondary structure prediction for aligned RNA sequences. , 2002, Journal of molecular biology.

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

[85]  G. Caetano-Anollés.  Tracing the evolution of RNA structure in ribosomes. , 2002, Nucleic acids research.

[86]  Cédric Feschotte,et al.  Plant transposable elements: where genetics meets genomics , 2002, Nature Reviews Genetics.

[87]  E. Wagner,et al.  Lead(II) as a probe for investigating RNA structure in vivo. , 2002, RNA.

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

[89]  Akira Sakamaki,et al.  using an , 2002 .

[90]  D. Ecker,et al.  RNAMotif, an RNA secondary structure definition and search algorithm. , 2001, Nucleic acids research.

[91]  P Schuster,et al.  Evolution in Silico and in Vitro: The RNA Model , 2001, Biological chemistry.

[92]  P. Moore.  1 – A Spectroscopist’s View of RNA Conformation: RNA Structural Motifs , 2001 .

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

[94]  Elena Rivas,et al.  Secondary structure alone is generally not statistically significant for the detection of noncoding RNAs , 2000, Bioinform..

[95]  A. Krogh,et al.  No evidence that mRNAs have lower folding free energies than random sequences with the same dinucleotide distribution. , 1999, Nucleic acids research.

[96]  R. Lück,et al.  ConStruct: a tool for thermodynamic controlled prediction of conserved secondary structure. , 1999, Nucleic acids research.

[97]  R R Breaker,et al.  Relationship between internucleotide linkage geometry and the stability of RNA. , 1999, RNA.

[98]  Ronald R. Breaker,et al.  Kinetics of RNA Degradation by Specific Base Catalysis of Transesterification Involving the 2‘-Hydroxyl Group , 1999 .

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

[100]  David W. Digby,et al.  mRNAs have greater negative folding free energies than shuffled or codon choice randomized sequences. , 1999, Nucleic acids research.

[101]  S. Eddy,et al.  A computational screen for methylation guide snoRNAs in yeast. , 1999, Science.

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

[103]  P. Moore.  6.02 – A Spectroscopist’s View of RNA Conformation: RNA Structural Motifs , 1999 .

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

[105]  S. Eddy,et al.  tRNAscan-SE: a program for improved detection of transfer RNA genes in genomic sequence. , 1997, Nucleic acids research.

[106]  Gabriele Varani,et al.  NMR investigation of RNA structure , 1996 .

[107]  R. Lück,et al.  Thermodynamic prediction of conserved secondary structure: application to the RRE element of HIV, the tRNA-like element of CMV and the mRNA of prion protein. , 1996, Journal of molecular biology.

[108]  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.

[109]  D. Crothers,et al.  In vivo structural analysis of spliced leader RNAs in Trypanosoma brucei and Leptomonas collosoma: a flexible structure that is independent of cap4 methylations. , 1995, RNA.

[110]  R. Durbin,et al.  RNA sequence analysis using covariance models. , 1994, Nucleic acids research.

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

[112]  R. Zwanzig,et al.  Levinthal's paradox. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[113]  C. Burks,et al.  Identifying potential tRNA genes in genomic DNA sequences. , 1991, Journal of molecular biology.

[114]  O. Kandler,et al.  Towards a natural system of organisms: proposal for the domains Archaea, Bacteria, and Eucarya. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[115]  Bruce A. Shapiro,et al.  A computational procedure for assessing the significance of RNA secondary structure , 1990, Comput. Appl. Biosci..

[116]  D. Turner,et al.  Improved predictions of secondary structures for RNA. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[117]  Jih-Hsiang Chen,et al.  A program for predicting significant RNA secondary structures , 1988, Comput. Appl. Biosci..

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

[119]  Clive Richards,et al.  The Blind Watchmaker , 1987, Bristol Medico-Chirurgical Journal.

[120]  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.

[121]  D. Sankoff.  Simultaneous Solution of the RNA Folding, Alignment and Protosequence Problems , 1985 .

[122]  T. Cech,et al.  Secondary structure of the circular form of the Tetrahymena rRNA intervening sequence: a technique for RNA structure analysis using chemical probes and reverse transcriptase. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[123]  Manolo Gouy,et al.  An energy model that predicts the correct folding of both the tRNA and the 5S RNA molecules , 1984, Nucleic Acids Res..

[124]  D. Sankoff,et al.  RNA secondary structures and their prediction , 1984 .

[125]  J. Ninio.  Prediction of pairing schemes in RNA molecules-loop contributions and energy of wobble and non-wobble pairs. , 1980, Biochimie.