Partition function and base pairing probabilities of RNA heterodimers

BackgroundRNA has been recognized as a key player in cellular regulation in recent years. In many cases, non-coding RNAs exert their function by binding to other nucleic acids, as in the case of microRNAs and snoRNAs. The specificity of these interactions derives from the stability of inter-molecular base pairing. The accurate computational treatment of RNA-RNA binding therefore lies at the heart of target prediction algorithms.MethodsThe standard dynamic programming algorithms for computing secondary structures of linear single-stranded RNA molecules are extended to the co-folding of two interacting RNAs.ResultsWe present a program, RNAcofold, that computes the hybridization energy and base pairing pattern of a pair of interacting RNA molecules. In contrast to earlier approaches, complex internal structures in both RNAs are fully taken into account. RNAcofold supports the calculation of the minimum energy structure and of a complete set of suboptimal structures in an energy band above the ground state. Furthermore, it provides an extension of McCaskill's partition function algorithm to compute base pairing probabilities, realistic interaction energies, and equilibrium concentrations of duplex structures.AvailabilityRNAcofold is distributed as part of the Vienna RNA Package, http://www.tbi.univie.ac.at/RNA/.ContactStephan H. Bernhart – berni@tbi.univie.ac.at

[1]  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.

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

[3]  Sonja J. Prohaska,et al.  Evolutionary patterns of non-coding RNAs , 2005, Theory in Biosciences.

[4]  M. Waterman Secondary Structure of Single-Stranded Nucleic Acidst , 1978 .

[5]  S. Eddy,et al.  Computational identification of non-coding RNAs in Saccharomyces cerevisiae by comparative genomics. , 2003, Nucleic acids research.

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

[7]  Christoph Flamm,et al.  Determination of thermodynamic parameters for HIV DIS type loop-loop kissing complexes. , 2004, Nucleic acids research.

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

[9]  P. Stadler,et al.  Mapping of conserved RNA secondary structures predicts thousands of functional noncoding RNAs in the human genome , 2005, Nature Biotechnology.

[10]  S. Eddy,et al.  Noncoding RNA genes identified in AT-rich hyperthermophiles , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[11]  Michael Zuker,et al.  Optimal computer folding of large RNA sequences using thermodynamics and auxiliary information , 1981, Nucleic Acids Res..

[12]  P. Smith Santa Fe, New Mexico , 1969 .

[13]  Thomas E. Royce,et al.  Global Identification of Human Transcribed Sequences with Genome Tiling Arrays , 2004, Science.

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

[15]  P. Stadler,et al.  The effect of RNA secondary structures on RNA-ligand binding and the modifier RNA mechanism: a quantitative model. , 2005, Gene.

[16]  J. Mattick Challenging the dogma: the hidden layer of non-protein-coding RNAs in complex organisms. , 2003, BioEssays : news and reviews in molecular, cellular and developmental biology.

[17]  Robert Giegerich,et al.  Design, implementation and evaluation of a practical pseudoknot folding algorithm based on thermodynamics , 2004, BMC Bioinformatics.

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

[19]  S. Cawley,et al.  Unbiased Mapping of Transcription Factor Binding Sites along Human Chromosomes 21 and 22 Points to Widespread Regulation of Noncoding RNAs , 2004, Cell.

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

[21]  G. Helt,et al.  Transcriptional Maps of 10 Human Chromosomes at 5-Nucleotide Resolution , 2005, Science.

[22]  R. Emeson,et al.  Functions and mechanisms of RNA editing. , 2000, Annual review of genetics.

[23]  S. Cawley,et al.  Novel RNAs identified from an in-depth analysis of the transcriptome of human chromosomes 21 and 22. , 2004, Genome research.

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

[25]  Volker A Erdmann,et al.  Local RNA target structure influences siRNA efficacy: systematic analysis of intentionally designed binding regions. , 2005, Journal of molecular biology.

[26]  M. Watzele,et al.  RNA stem-loop enhanced expression of previously non-expressible genes. , 2004, Nucleic acids research.

[27]  Peter F. Stadler,et al.  Non-coding RNAs in Ciona intestinalis , 2005, ECCB/JBI.

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

[29]  A. Condon,et al.  Secondary structure prediction of interacting RNA molecules. , 2005, Journal of molecular biology.

[30]  J. SantaLucia,et al.  A unified view of polymer, dumbbell, and oligonucleotide DNA nearest-neighbor thermodynamics. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[31]  C. Kidner,et al.  The developmental role of microRNA in plants. , 2005, Current opinion in plant biology.

[32]  David Sankoff,et al.  RNA secondary structures and their prediction , 1984 .

[33]  O. Hobert Common logic of transcription factor and microRNA action. , 2004, Trends in biochemical sciences.

[34]  Peter F. Stadler,et al.  Genome-wide mapping of conserved RNA Secondary Structures Reveals Evidence for Thousands of functional Non-Coding RNAs in Human , 2022 .

[35]  Zissimos Mourelatos,et al.  The microRNA world: small is mighty. , 2003, Trends in biochemical sciences.

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

[37]  M. Zuker,et al.  Prediction of hybridization and melting for double-stranded nucleic acids. , 2004, Biophysical journal.

[38]  D. Bartel,et al.  Micromanagers of gene expression: the potentially widespread influence of metazoan microRNAs , 2004, Nature Reviews Genetics.

[39]  Naoki Sugimoto,et al.  Temperature dependence of thermodynamic properties for DNA/DNA and RNA/DNA duplex formation. , 2002, European journal of biochemistry.

[40]  Jörg Hackermüller,et al.  mRNA Openers and Closers: Modulating AU‐Rich Element‐Controlled mRNA Stability by a Molecular Switch in mRNA Secondary Structure , 2004, Chembiochem : a European journal of chemical biology.

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

[42]  K. Stuart,et al.  RNA editing in kinetoplastid protozoa , 1991, Current opinion in genetics & development.

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

[44]  O. Uhlenbeck,et al.  A coat for all sequences , 1998, Nature Structural Biology.

[45]  Peter F. Stadler,et al.  Thermodynamics of RNA-RNA Binding , 2006, German Conference on Bioinformatics.

[46]  Jerrold R. Griggs,et al.  Algorithms for Loop Matchings , 1978 .

[47]  Michael Zuker,et al.  Mfold web server for nucleic acid folding and hybridization prediction , 2003, Nucleic Acids Res..

[48]  D. Corey,et al.  Intracellular inhibition of hepatitis C virus (HCV) internal ribosomal entry site (IRES)-dependent translation by peptide nucleic acids (PNAs) and locked nucleic acids (LNAs). , 2004, Nucleic acids research.

[49]  T. Tuschl,et al.  RNA interference is mediated by 21- and 22-nucleotide RNAs. , 2001, Genes & development.

[50]  V. Ambros The functions of animal microRNAs , 2004, Nature.

[51]  John G Doench,et al.  Specificity of microRNA target selection in translational repression. , 2004, Genes & development.

[52]  S. Eddy,et al.  Computational identification of noncoding RNAs in E. coli by comparative genomics , 2001, Current Biology.

[53]  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.

[54]  Douglas H. Turner,et al.  Oligonucleotide directed misfolding of RNA inhibits Candida albicans group I intron splicing , 2002, Proceedings of the National Academy of Sciences of the United States of America.