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Comparative Genomics pp 363–400Cite as

Comparative RNA Genomics

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 1704))

Abstract

Over the last two decades it has become clear that RNA is much more than just a boring intermediate in protein expression. Ancient RNAs still appear in the core information metabolism and comprise a surprisingly large component in bacterial gene regulation. A common theme with these types of mostly small RNAs is their reliance of conserved secondary structures. Large scale sequencing projects, on the other hand, have profoundly changed our understanding of eukaryotic genomes. Pervasively transcribed, they give rise to a plethora of large and evolutionarily extremely flexible noncoding RNAs that exert a vastly diverse array of molecule functions. In this chapter we provide a—necessarily incomplete—overview of the current state of comparative analysis of noncoding RNAs, emphasizing computational approaches as a means to gain a global picture of the modern RNA world.

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References

  1. Kapranov P, Willingham AT, Gingeras TR (2007) Genome-wide transcription and the implications for genomic organization. Nat Rev Genet 8:413–423

    Article  CAS  PubMed  Google Scholar 

  2. Carninci P, FANTOM Consortium (2005) The transcriptional landscape of the mammalian genome. Science 309:1559–1563

    Article  CAS  Google Scholar 

  3. ENCODE Project Consortium (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489:57–74

    Article  CAS  Google Scholar 

  4. Derrien T, Johnson R, Bussotti G, Tanzer A, Djebali S, Tilgner H, Guernec G, Martin D, Merkel A, Knowles DG, Lagarde J, Veeravalli L, Ruan X, Ruan Y, Lassmann T, Carninci P, Brown JB, Lipovich L, Gonzalez JM, Thomas M, Davis CA, Shiekhattar R, Gingeras TR, Hubbard TJ, Notredame C, Harrow J, Guigó R (2012) The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res 22:1775–1789

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Clark MB, Amaral PP, Schlesinger FJ, Dinger ME, Taft RJ, Rinn JL, Ponting CP, Stadler PF, Morris KJ, Morillon A, Rozowsky JS, Gerstein M, Wahlestedt C, Hayashizaki Y, Carninci P, Gingeras TR, Mattick JS (2011) The reality of pervasive transcription. PLoS Biol 9:e1000625

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Tisseur M, Kwapisz M, Morillon A (2011) Pervasive transcription – lessons from yeast. Biochimie 93:1889–1896

    Article  CAS  PubMed  Google Scholar 

  7. Wu J, Delneri D, O’Keefe RT (2012) Non-coding RNAs in Saccharomyces cerevisiae: what is the function? Biochem Soc Trans 40:907–911

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Leong HS, Dawson K, Wirth C, Li Y, Wirth Y, Smith DL, Wilkinson CRM, Miller CJ (2014) A global non-coding RNA system modulates fission yeast protein levels in response to stress. Nat Commun 5:3947

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Xuan H, Zhang L, Liu X, Han G, Li J, Li X, Liu A, Liao M, Zhang S (2015) PLNlncRbase: a resource for experimentally identified lncRNAs in plants. Gene 573:328–332

    Article  CAS  PubMed  Google Scholar 

  10. Woehle C, Kusdian G, Radine C, Graur D, Landan G, Gould SB (2014) The parasite Trichomonas vaginalis expresses thousands of pseudogenes and long non-coding RNAs independently from functional neighbouring genes. BMC Genomics 15:906

    Article  PubMed  PubMed Central  Google Scholar 

  11. Sharma CM, Hoffmann S, Darfeuille F, Reignier J, Findeiß S, Sittka A, Chabas S, Reiche K, Hackermüller J, Reinhardt RR, Stadler PF, Vogel J (2010) The primary transcriptome of the major human pathogen Helicobacter pylori. Nature 464:250–255

    Article  CAS  PubMed  Google Scholar 

  12. Lybecker M, Bilusic I, Raghavan R (2014) Pervasive transcription: detecting functional RNAs in bacteria. Transcription 5:e944039

    Article  PubMed  PubMed Central  Google Scholar 

  13. Wade JT, Grainger DC (2014) Pervasive transcription: illuminating the dark matter of bacterial transcriptomes. Nat Rev Microbiol 12:647–653

    Article  CAS  PubMed  Google Scholar 

  14. Perkel JM (2013) Visiting “noncodarnia”. BioTechniques 54(6):303–304

    Article  CAS  Google Scholar 

  15. Mercer TR, Dinger ME, Mattick JS (2009) Long non-coding RNAs: insights into functions. Nat Rev Genet 10(3):155–159

    Article  CAS  PubMed  Google Scholar 

  16. Wassarman KM, Repoila F, Rosenow C, Storz G, Gottesman S (2001) Identification of novel small RNAs using comparative genomics and microarrays. Genes Dev. 15(13):1637–1651

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Marz M, Gruber AR, Siederdissen CH, Amman F, Badelt S, Bartschat S, Bernhart SH, Beyer S, Kehr W, Lorenz R, Tanzer A, Yusuf D, Tafer H, Hofacker IL, Stadler PF (2011) Animal snoRNAs and scaRNAs with exceptional structures. RNA Biol 8:938–946

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Bompfünewerer AF, Flamm C, Fried C, Fritzsch G, Hofacker IL, Lehmann J, Missal K, Mosig A, Müller B, Prohaska SJ, Stadler BMR, Stadler PF, Tanzer A, Washietl S, Witwer C (2005) Evolutionary patterns of non-coding RNAs. Theory Biosci. 123:301–369

    Article  PubMed  CAS  Google Scholar 

  19. The Athanasius F. Bompfünewerer RNA Consortium, Backofen R, Flamm C, Fried C, Fritzsch G, Hackermüller J, Hertel J, Hofacker IL, Missal K, Mosig SJ, Prohaska A, Rose D, Stadler PF, Tanzer A, Washietl S, Sebastian W (2007) RNAs everywhere: genome-wide annotation of structured RNAs. J Exp Zool B: Mol Dev Evol 308B:1–25

    Google Scholar 

  20. Hertel J, Stadler PF (2015) The expansion of animal microRNA families revisited. Life 5:905–920

    Google Scholar 

  21. Brown JW, Echeverria M, Qu LH (2003) Plant snoRNAs: functional evolution and new modes of gene expression. Trends Plant Sci 8:42–49

    Article  CAS  PubMed  Google Scholar 

  22. Kehr S, Bartschat S, Tafer H, Stadler PF, Hertel J (2014) Matching of soulmates: coevolution of snoRNAs and their targets. Mol Biol Evol 31:455–467

    Article  CAS  PubMed  Google Scholar 

  23. Jorjani H, Kehr S, Jedlinski DJ, Gumienny R, Hertel J, Stadler PF, Zavolan M, Gruber AR (2016) An updated human snoRNAome. Nucleic Acids Res 44(11):5068–5082

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Bhattacharya DP, Bartschat S, Kehr S, Hertel J, Grosse I, Stadler PF (2016) Phylogenetic distribution of plant snoRNA families. BMC Genomics 17:969

    Article  Google Scholar 

  25. Gorodkin J, Ruzzo WL (2014) RNA sequence, structure, and function: computational and bioinformatic methods. In: Methods in molecular biology, vol 1097. Humana Press/Springer, New York

    Google Scholar 

  26. Fontana W, Stadler PF, Bornberg-Bauer EG, Griesmacher T, Hofacker IL, Tacker M, Tarazona P, Weinberger ED, Schuster P (1993) RNA folding landscapes and combinatory landscapes. Phys Rev E 47:2083–2099

    Article  CAS  Google Scholar 

  27. Schuster P, Fontana W, Stadler PF, Hofacker IL (1994) From sequences to shapes and back: a case study in RNA secondary structures. Proc R Soc Lond B 255:279–284

    Article  CAS  Google Scholar 

  28. Nussinov R, Pieczenik G, Griggs JR, Kleitman DJ (1978) Algorithms for loop matchings. SIAM J Appl Math 35(1):68–82

    Article  Google Scholar 

  29. Zuker M, Stiegler P (1981) Optimal computer folding of large RNA sequences using thermodynamics and auxilary information. Nucleic Acids Res 9(1):133–147

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Zuker M (1989) On finding all suboptimal foldings of an RNA molecule. Science 244:48–52

    Article  CAS  PubMed  Google Scholar 

  31. Wuchty S, Fontana W, Hofacker IL, Schuster P (1999) Complete suboptimal folding of RNA and the stability of secondary structures. Biopolymers 49:145–165

    Article  CAS  PubMed  Google Scholar 

  32. McCaskill JS (1990) The equilibrium partition function and base pair binding probabilities for RNA secondary structure. Biopolymers 29(6–7):1105–1119

    Article  CAS  PubMed  Google Scholar 

  33. Ding Y, Lawrence CE (2001) Statistical prediction of single-stranded regions in RNA secondary structure and application to predicting effective antisense target sites and beyond. Nucleic Acids Res 29(5):1034–1046

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Hofacker IL, Fekete M, Stadler PF (2002) Secondary structure prediction for aligned RNA sequences. J Mol Biol 319:1059–1066

    Article  CAS  PubMed  Google Scholar 

  35. Bernhart SH, Hofacker IL, Will S, Gruber AR, Stadler PF (2008) RNAalifold: improved consensus structure prediction for RNA alignments. BMC Bioinf 9:474

    Article  CAS  Google Scholar 

  36. Knudsen B, Hein J (2003) Pfold: RNA secondary structure prediction using stochastic context-free grammars. Nucleic Acids Res 31(13):3423–3428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Sükösd Z, Knudsen B, Kjems J, Pedersen CN (2012) PPfold 3.0: fast RNA secondary structure prediction using phylogeny and auxiliary data. Bioinformatics 28:2691–2692

    Article  PubMed  CAS  Google Scholar 

  38. Seemann SE, Gorodkin J, Backofen R (2008) Unifying evolutionary and thermodynamic information for RNA folding of multiple alignments. Nucleic Acids Res 36(20):6355–6362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Klein RJ, Misulovin Z, Eddy SR (2002) Noncoding RNA genes identified in AT-rich hyperthermophiles. Proc Natl Acad Sci USA 99:7542–7547

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Larsson P, Hinas A, Ardell DH, Kirsebom LA, Virtanen A, Söderbom F (2008) De novo search for non-coding RNA genes in the AT-rich genome of Dictyostelium discoideum: performance of Markov-dependent genome feature scoring. Genome Res 18:888–899

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Haerty W, Ponting CP (2015) Unexpected selection to retain high GC content and splicing enhancers within exons of multiexonic lncRNA loci. RNA 21:333–346

    Article  PubMed  CAS  Google Scholar 

  42. Washietl S, Hofacker IL (2004) Consensus folding of aligned sequences as a new measure for the detection of functional RNAs by comparative genomics. J Mol Biol 342:19–30

    Article  CAS  PubMed  Google Scholar 

  43. Washietl S, Hofacker IL, Stadler PF (2005) Fast and reliable prediction of noncoding RNAs. Proc Natl Acad Sci USA 102:2454–2459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Clote P, Ferré F, Kranakis E, Krizanc D (2005) Structural RNA has lower folding energy than random RNA of the same dinucleotide frequency. RNA 11:578–591

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Workman C, Krogh A (1999) No evidence that mRNAs have lower folding free energies than random sequences with the same dinucleotide distribution. Nucleic Acids Res 27:4816–4822

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Altschul SF, Erickson BW (1985) Significance of nucleotide sequence alignment: a method for random sequence permutation that preserves dinucleotide and codon usage. Mol Biol Evol 2:526–538

    CAS  PubMed  Google Scholar 

  47. Fitch WM (1983) Random sequences. J Mol Biol 163:171–176

    Article  CAS  PubMed  Google Scholar 

  48. Kandel D, Matias Y, Unger R, Winker P (1996) Shuffling biological sequences. Discr Appl Math 71:171–185

    Article  Google Scholar 

  49. Jiang M, Anderson J, Gillespie J, Joel M (2008) uShuffle: a useful tool for shuffling biological sequences while preserving the k-let counts. BMC Bioinformatics 9:192

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Gruber AR, Findeiß S, Washietl S, Hofacker IL, Stadler PF (2010) RNAz 2.0: improved noncoding RNA detection. Pac Symp Biocomput 15:69–79

    Google Scholar 

  51. Soldatov RA, Vinogradova SV, Mironov AA (2014) RNASurface: fast and accurate detection of locally optimal potentially structured RNA segments. Bioinformatics 30:457–463

    Article  CAS  PubMed  Google Scholar 

  52. Washietl S (2005) Prediction of structured non-coding RNAs by comparative sequence analysis. PhD thesis, Univsity of Vienna

    Google Scholar 

  53. van Nimwegen E, Crutchfield JP, Huynen M (1999) Neutral evolution of mutational robustness. Proc Natl Acad Sci USA 96:9716–9720

    Article  PubMed  PubMed Central  Google Scholar 

  54. Wagner A, Stadler PF (1999) Viral RNA and evolved mutational robustness. J Exp Zool MDE 285:119–127

    Article  CAS  Google Scholar 

  55. Ancel LW, Fontana W (2000) Plasticity, evolvability, and modularity in RNA. J Exp Zool MDE 288:242–283

    Article  CAS  Google Scholar 

  56. Borenstein E, Ruppin E (2006) Direct evolution of genetic robustness in microRNA. Proc Natl Acad Sci USA 103:6593–6598

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Pei S, Anthony JS, Meyer MM (2015) Sampled ensemble neutrality as a feature to classify potential structured RNAs. BMC Genomics 16:35

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Gruber AR, Bernhart SH, Hofacker IL, Washietl S (2008) Strategies for measuring evolutionary conservation of RNA secondary structures. BMC Bioinf 9:122

    Article  CAS  Google Scholar 

  59. Salari R, Kimchi-Sarfaty C, Gottesman MM, Przytycka TM (2013) Sensitive measurement of single-nucleotide polymorphism-induced changes of RNA conformation: application to disease studies. Nucleic Acids Res 41:44–53

    Article  CAS  PubMed  Google Scholar 

  60. Sabarinathan R, Tafer H, Seemann SE, Hofacker IL, Stadler PF, Gorodkin J (2013) RNAsnp: efficient detection of local RNA secondary structure changes induced by SNPs. Hum Mut 34:546–556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Gardner PP, Wilm A, Washietl S (2005) A benchmark of multiple sequence alignment programs upon structural RNAs. Nucleic Acids Res 33:2433–2439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Parsch J, Braverman JM, Stephan W (2000) Comparative sequence analysis and patterns of covariation in RNA secondary structures. Genetics 154:909–921

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Coventry A, Kleitman DJ, Berger B (2004) MSARI: multiple sequence alignments for statistical detection of RNA secondary structure. Proc Natl Acad Sci USA 101:12102–12107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. di Bernardo D, Down T, Hubbard T (2003) ddbRNA: detection of conserved secondary structures in multiple alignments. Bioinformatics 19:1606–1611

    Article  PubMed  Google Scholar 

  65. Seemann SE, Richter AS, Gorodkin J, Backofen R (2010) Hierarchical folding of multiple sequence alignments for the prediction of structures and RNA-RNA interactions. Algorithms Mol Biol 5:22

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Seemann SE, Mirza AH, Hansen C, Bang-Berthelsen CH, Garde C, Christensen-Dalsgaard M, Torarinsson E, Yao Z, Workman C, Pociot H, Nielsen F, Tommerup N, Ruzzo WL, Gorodkin J (2017) The identification and functional annotation of RNA structures conserved in vertebrates. Genome Res 27(8):1371–1383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Lindgreen S, Gardner PP, Krogh A (2006) Measuring covariation in RNA alignments: physical realism improves information measures. Bioinformatics 22:2988–2995

    Article  CAS  PubMed  Google Scholar 

  68. Menzel P, Seemann SE, Gorodkin J (2012) RILogo: visualizing RNA-RNA interactions. Bioinformatics 28(19):2523–2526

    Article  CAS  PubMed  Google Scholar 

  69. Piskol R, Stephan W (2011) Selective constraints in conserved folded RNAs of Drosophilid and Hominid genomes. Mol Biol Evol 28:1519–1529

    Article  CAS  PubMed  Google Scholar 

  70. Kusumi J, Ichinose M, Takefu M, Piskol R, Stephan W, Iizuka M (2016) A model of compensatory molecular evolution involving multiple sites in RNA molecules. J Theor Biol 388:96–107

    Article  CAS  PubMed  Google Scholar 

  71. Ponjavic J, Ponting CP, Lunter G (2007) Functionality or transcriptional noise? Evidence for selection within long noncoding RNAs. Genome Res 17:556–565

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Pang KC, Frith MC, Mattick JS (2006) Rapid evolution of noncoding RNAs: lack of conservation does not mean lack of function. Trends Genet 22:1–5

    Article  CAS  PubMed  Google Scholar 

  73. Marques AC, Ponting CP (2009) Catalogues of mammalian long noncoding RNAs: modest conservation and incompleteness. Genome Biol 10:R124

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, Huarte M, Zuk O, Carey BW, Cassady JP, Cabili MN, Jaenisch R, Mikkelsen TS, Jacks T, Hacohen N, Bernstein BE, Kellis M, Regev A, Rinn JL, Lander ES (2009) Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 458:223–227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Managadze D, Lobkovsky AE, Wolf YI, Shabalina SA, Rogozin IB, Koonin EV (2013) The vast, conserved mammalian lincRNome. PLoS Comput Biol 9:e1002917

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Hüttenhofer A, Schattner P, Polacek N (2005) Non-coding RNAs: hope or hype? Trends Genet 21:289–297

    Article  PubMed  CAS  Google Scholar 

  77. Palazzo AF, Lee ES (2015) Non-coding RNA: what is functional and what is junk? Front Genet 6:2

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Johnsson P, Lipovich L, Grandér D, Morris KV (2014) Evolutionary conservation of long non-coding RNAs: sequence, structure, function. Biochim Biophys Acta 1840:1063–1071

    Article  CAS  PubMed  Google Scholar 

  79. Schüler A, Ghanbarian AT, Hurst LD (2014) Purifying selection on splice-related motifs, not expression level nor RNA folding, explains nearly all constraint on human lincRNAs. Mol Biol Evol 31:3164–3183

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  80. Mercer TR, Mattick JS (2013) Structure and function of long noncoding RNAs in epigenetic regulation. Nat Struct Mol Biol 20:300–307

    Article  CAS  PubMed  Google Scholar 

  81. Smith MA, Gesell T, Stadler PF, Mattick JS (2013) Widespread purifying selection on RNA structure in mammals. Nucleic Acids Res 41:8220–8236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Hezroni H, Koppstein D, Schwartz MG, Avrutin A, Bartel DP, Ulitsky I (2015) Principles of long noncoding RNA evolution derived from direct comparison of transcriptomes in 17 species. Cell 11:1110–1122

    CAS  Google Scholar 

  83. Washietl S, Kellis M, Garber M (2014) Evolutionary dynamics and tissue specificity of human long noncoding RNAs in six mammals. Genome Res 24:616–628

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Kutter C, Watt S, Stefflova K, Wilson MD, Goncalves A, Ponting CP, Odom DT, Marques AC (2012) Rapid turnover of long noncoding RNAs and the evolution of gene expression. PLoS Genet 8:e1002841

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Necsulea A, Soumillon M, Warnefors M, Liechti A, Daish T, Zeller U, Baker J, Grützner F, Kaessmann H (2014) The evolution of lncRNA repertoires and expression patterns in tetrapods. Nature 505:635–640

    Article  CAS  PubMed  Google Scholar 

  86. Ward M, McEwan C, Mill JD, Janitz M (2015) Conservation and tissue-specific transcription patterns of long noncoding RNAs. J Hum Transcr 1:2–9

    Article  PubMed  PubMed Central  Google Scholar 

  87. Ulitsky I, Shkumatava A, Jan CH, Sive H, Bartel DP (2011) Conserved function of lincRNAs in vertebrate embryonic development despite rapid sequence evolution. Cell 147:1537–1550

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Young RS, Marques AC, Tibbit C, Haerty W, Bassett AR, Liu JL, Ponting CP (2012) Identification and properties of 1,119 candidate lincRNA loci in the Drosophila melanogaster genome. Genome Biol Evol 4:427–442

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Nitsche A, Rose D, Fasold M, Reiche K, Stadler PF (2015) Comparison of splice sites reveals that long non-coding RNAs are evolutionarily well conserved. RNA 21:801–812

    Google Scholar 

  90. Eng L, Coutinho G, Nahas S, Yeo G, Tanouye R, Babaei M, Dörk T, Burge C, Gatti RA (2004) Nonclassical splicing mutations in the coding and noncoding regions of the ATM gene: maximum entropy estimates of splice junction strengths. Hum Mutat 23:67–76

    Article  CAS  PubMed  Google Scholar 

  91. Canzler S, Stadler PF, Hertel J (2016) U6 snRNA intron insertion occurred multiple times during fungi evolution. RNA Biol 13:119–127

    Google Scholar 

  92. Louhichi A, Fourati A, Rebaï A (2011) IGD: a resource for intronless genes in the human genome. Gene 488:35–40

    Article  CAS  PubMed  Google Scholar 

  93. Nakaya HI, Amaral PP, Louro R, Lopes A, Fachel AA, Moreira YB, El-Jundi TA, da Silva AM, Reis EM, Verjovski-Almeida S (2007) Genome mapping and expression analyses of human intronic noncoding RNAs reveal tissue-specific patterns and enrichment in genes related to regulation of transcription. Genome Biol 8:R43

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  94. Louro R, Nakaya HI, Amaral PP, Festa F, Sogayar MC, da Silva AM, Verjovski-Almeida S, Reis EM (2007) Androgen responsive intronic non-coding RNAs. BMC Biol 5:4

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. Louro R, El-Jundi T, Nakaya HI, Reis EM, Verjovski-Almeida S (2008) Conserved tissue expression signatures of intronic noncoding RNAs transcribed from human and mouse loci. Genomics 92:18–25

    Article  CAS  PubMed  Google Scholar 

  96. Engelhardt J, Stadler PF (2012) Hidden treasures in unspliced EST data. Theory Biosci 131:49–57.

    Google Scholar 

  97. Rinn JL, Euskirchen G, Bertone P, Martone R, Luscombe NM, Hartman S, Harrison PM, Nelson FK, Miller P, Gerstein M, Weissman S, Snyder M (2003) The transcriptional activity of human chromosome 22. Genes Dev 17:529–540

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Reis EM, Nakaya HI, Louro R, Canavez FC, Flatschart AV, Almeida GT, Egidio CM, Paquola AC, Machado AA, Festa F, Yamamoto D, Alvarenga R, da Silva CC, Brito GC, Simon SD, Moreira-Filho CA, Leite KR, Camara-Lopes LH, Campos FS, Gimba E, Vignal GM, El-Dorry H, Sogayar MC, Barcinski MA, da Silva AM, Verjovski-Almeida S (2004) Antisense intronic non-coding RNA levels correlate to the degree of tumor differentiation in prostate cancer. Oncogene 23:6684–6692

    Article  CAS  PubMed  Google Scholar 

  99. Beckedorff FC, Ayupe AC, Crocci-Souza R, Amaral MS, Nakaya HI, Soltys DT, Menck CFM, Reis EM, Verjovski-Almeida S (2013) The intronic long noncoding RNA ANRASSF1 recruits PRC2 to the RASSF1A promoter, reducing the expression of RASSF1A and increasing cell proliferation. PLoS Genet 9:e1003705

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Sasaki YTF, Ideue T, Sano M, Mituyama T, Hirose T (2009) MENε/β noncoding RNAs are essential for structural integrity of nuclear paraspeckles. Proc Natl Acad Sci USA 106:2525–2530

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Sunwoo H, Dinger ME, Wilusz JE, Amaral PP, Mattick JS, Spector DL (2009) MEN ε/β nuclear-retained non-coding RNAs are up-regulated upon muscle differentiation and are essential components of paraspeckles. Genome Res 19:347–359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Mao YS, Sunwoo H, Zhang B, Spector DL (2011) Direct visualization of the co-transcriptional assembly of a nuclear body by noncoding RNAs. Nat Cell Biol 13:95–101

    Article  CAS  PubMed  Google Scholar 

  103. Stadler PF (2010) Evolution of the long non-coding RNAs MALAT1 and MENβ/ε. In: Ferreira CE, Miyano S, Stadler PF (eds.) Advances in bioinformatics and computational biology, 5th brazilian symposium on bioinformatics. Lecture notes in computer science, vol 6268. Springer, Heidelberg, pp 1–12

    Google Scholar 

  104. Chung S, Nakagawa H, Uemura M, Piao L, Ashikawa K, Hosono N, Takata R, Akamatsu S, Kawaguchi T, Morizono T, Tsunoda T, Daigo Y, Matsuda K, Kamatani N, Nakamura Y, Kubo M (2011) Association of a novel long non-coding RNA in 8q24 with prostate cancer susceptibility. Cancer Sci 102:245–252

    Article  CAS  PubMed  Google Scholar 

  105. Hackermüller J, Reiche K, Otto C, Hösler N, Blumert C, Brocke-Heidrich K, Böhlig L, Nitsche A, Kasack K, Ahnert P, Krupp W, Engeland K, Stadler PF, Horn F (2014) Cell cycle, oncogenic and tumor suppressor pathways regulate numerous long and macro non-protein coding RNAs. Genome Biol 15:R48

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  106. Kapranov P, St Laurent G, Raz T, Ozsolak F, Reynolds CP, Sorensen PH, Reaman G, Milos P, Arceci RJ, Thompson JF, Triche TJ (2010) The majority of total nuclear-encoded non-ribosomal RNA in a human cell is ‘dark matter’ un-annotated RNA. BMC Biol 8:149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Seidl CIM, Stricker SH, Barlow DP (2006) The imprinted Air ncRNA is an atypical RNAPII transcript that evades splicing and escapes nuclear export. EMBO J 25:1–11

    Article  CAS  Google Scholar 

  108. Stricker SH, Steenpass L, Pauler FM, Santoro F, Latos PA, Huang R, Koerner MV, Sloane MA, Warczok KE, Barlow DP (2008) Silencing and transcriptional properties of the imprinted Airn ncRNA are independent of the endogenous promoter. EMBO J 27:3116–3128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Redrup L, Branco MR, Perdeaux ER, Krueger C, Lewis A, Santos F, Nagano T, Cobb BS, Fraser P, Reik W (2009) The long noncoding RNA Kcnq1ot1 organises a lineage-specific nuclear domain for epigenetic gene silencing. Development 136:525–530

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Mercer TR, Wilhelm D, Dinger ME, Soldà G, Korbie DJ, Glazov EA, Truong V, Schwenke M, Simons C, Matthaei KI, Saint R, Koopman P, Mattick JS (2011) Expression of distinct RNAs from 3’ untranslated regions. Nucleic Acids Res 39:2393–2403

    Article  CAS  PubMed  Google Scholar 

  111. Engelhardt J, Stadler PF (2015) Evolution of the unspliced transcriptome. BMC Evol Biol 15:166

    Google Scholar 

  112. Menzel P, Gorodkin J, Stadler PF (2009) The tedious task of finding homologous non-coding RNA genes. RNA 15:2075–2082

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Nawrocki EP, Burge SW, Bateman A, Daub J, Eberhardt RY, Eddy SR, Floden EW, Gardner PP, Jones TA, Tate J, Finn RD (2015) Rfam 12.0: updates to the RNA families database. Nucl Acids Res 43:D130–D137

    Article  CAS  PubMed  Google Scholar 

  114. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) Basic local alignment search tool. J Mol Biol 215:403–410

    Article  CAS  PubMed  Google Scholar 

  115. Hertel J, de Jong D, Marz M, Rose D, Tafer H, Tanzer A, Schierwater B, Stadler PF (2009) Non-coding RNA annotation of the genome of Trichoplax adhaerens. Nucleic Acids Res 37:1602–1615

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Menzel P, Stadler PF, Gorodkin J (2011) maxAlike: maximum-likelihood based sequence reconstruction with application to improved primer design for unknown sequences. Bioinformatics 27:317–325

    Article  CAS  PubMed  Google Scholar 

  117. Xie M, Mosig A, Qi X, Li Y, Stadler PF, Chen J-L (2008) Size variation and structural conservation of vertebrate telomerase RNA. J Biol Chem 283:2049–2059

    Google Scholar 

  118. Lu Y, Sze S-H (2009) Improving accuracy of multiple sequence alignment algorithms based on alignment of neighboring residues. Nucl. Acids Res 37:463–472

    Article  CAS  Google Scholar 

  119. Bussotti G, Raineri E, Erb I, Zytnicki M, Wilm A, Beaudoing E, Bucher P, Notredame C (2011) BlastR-fast and accurate database searches for non-coding RNAs. Nucleic Acids Res 39:6886–6895

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Mosig A, Sameith K, Stadler PF (2005) fragrep: efficient search for fragmented patterns in genomic sequences. Geno Prot Bioinfo 4:56–60

    Article  Google Scholar 

  121. Weinberg Z, Ruzzo WL (2004) Exploiting conserved structure for faster annotation of non-coding RNAs without loss of accuracy. Bioinformatics 20:i334–i341

    Article  CAS  PubMed  Google Scholar 

  122. Weinberg Z, Ruzzo WL (2006) Sequence-based heuristics for faster annotation of non-coding RNA families. Bioinformatics 22:35–39

    Article  CAS  PubMed  Google Scholar 

  123. Lowe TM, Eddy SR (1997) tRNAscan-SE: a program for improved detection of transfer RNA genes in genomic sequence. Nucleic Acids Res 25:955–964

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Macke TJ, Ecker DJ, Gutell RR, Gautheret D, Case DA, Sampath R (2001) RNAMotif, an RNA secondary structure definition and search algorithm. Nucl Acids Res 29:4724–4735

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Billoud B, Kontic M, Viari A (1996) Palingol: a declarative programming language to describe nucleic acids’ secondary structures and to scan sequence database. Nucl Acids Res 24:1395–1403

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Gautheret D, Major F, Cedergren R (1990) Pattern searching/alignment with RNA primary and secondary structures: an effective descriptor for tRNA. Comput Appl Biosci 6:325–331

    CAS  PubMed  Google Scholar 

  127. Dsouza M, Larsen N, Overbeek R (1997) Searching for patterns in genomic data. Trends Genet 13:497–498

    Article  CAS  PubMed  Google Scholar 

  128. Reeder J, Reeder J, Giegerich R (2007) Locomotif: from graphical motif description to RNA motif search. Bioinformatics 23:i392–i400

    Article  CAS  PubMed  Google Scholar 

  129. Gautheret D, Lambert A (2001) Direct RNA motif definition and identification from multiple sequence alignments using secondary structure profiles. J Mol Biol 313:1003–1011

    Article  CAS  PubMed  Google Scholar 

  130. Freyhult EK, Bollback JP, Gardner PP (2007) Exploring genomic dark matter: a critical assessment of the performance of homology search methods on noncoding RNA. Genome Res 17:117–125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Finn RD, Coggill P, Eberhardt RY, Eddy SR, Mistry J, Mitchell AL, Potter SC, Punta M, Qureshi M, Sangrador-Vegas A, Salazar GA, Tate J, Bateman A (2016) The Pfam protein families database: towards a more sustainable future. Nucleic Acids Res 44(D1):D279–D285

    Article  CAS  PubMed  Google Scholar 

  132. Giegerich R (2014) Introduction to stochastic context free grammars. Methods Mol Biol 1097:85–106

    Article  CAS  PubMed  Google Scholar 

  133. Sükösd Z, Andersen ES, Lyngsø R (2014) SCFGs in RNA secondary structure prediction RNA secondary structure prediction: a hands-on approach. Methods Mol Biol 1097:143–162

    Article  PubMed  CAS  Google Scholar 

  134. Nawrocki EP, Eddy SR (2013) Infernal 1.1: 100-fold faster RNA homology searches. Bioinformatics 29:2933–2935

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Nawrocki EP (2014) Annotating functional RNAs in genomes using Infernal. Methods Mol Biol 1097:163–197

    Article  CAS  PubMed  Google Scholar 

  136. Anthon C, Tafer H, Havgaard JH, Thomsen B, Hedegaard J, Seemann SE, Pundhir S, Kehr S, Bartschat S, Nielsen M, Nielsen RO, Fredholm M, Stadler PF, Gorodkin J (2014) Structured RNAs and synteny regions in the pig genome. BMC Genomics 15:459

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  137. Eggenhofer F, Hofacker IL, Siederdissen CH (2016) RNAlien - unsupervised RNA family model construction. Nucl Acids Res 44:8433–8441

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Gesell T, Washietl S (2008) Dinucleotide controlled null models for comparative RNA gene prediction. BMC Bioinf 9:248

    Article  CAS  Google Scholar 

  139. Washietl S, Hofacker IL, Lukasser M, Hüttenhofer A, Stadler PF (2005) Mapping of conserved RNA secondary structures predicts thousands of functional non-coding RNAs in the human genome. Nat Biotech 23:1383–1390

    Article  CAS  Google Scholar 

  140. Rivas E, Eddy SR (2001) Noncoding RNA gene detection using comparative sequence analysis. BMC Bioinf 2:8

    Article  CAS  Google Scholar 

  141. Pedersen JS, Bejerano G, Siepel A, Rosenbloom K, Lindblad-Toh K, Lander ES, Kent J, Miller W, Haussler D (2006) Identification and classification of conserved RNA secondary structures in the human genome. PLoS Comput Biol 2(4):e33

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Parker BJ, Moltke I, Roth A, Washietl S, Wen J, Kellis M, Breaker R, Pedersen JS (2011) New families of human regulatory RNA structures identified by comparative analysis of vertebrate genomes. Genome Res 21(11):1929–1943

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Wang AX, Ruzzo WL, Tompa M (2007) How accurately is ncRNA aligned within whole-genome multiple alignments? BMC Bioinf 8:417

    Article  CAS  Google Scholar 

  144. Gorodkin J, Stricklin SL, Stormo GD (2001) Discovering common stem-loop motifs in unaligned RNA sequences. Nucleic Acids Res 29:2135–2144

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Havgaard JH, Torarinsson E, Gorodkin J (2007) Fast pairwise structural RNA alignments by pruning of the dynamical programming matrix. PLoS Comput Biol 3(10):1896–1908

    Article  CAS  PubMed  Google Scholar 

  146. Sundfeld D, Havgaard JH, de Melo AC, Gorodkin J (2016) Foldalign 2.5: multithreaded implementation for pairwise structural RNA alignment. Bioinformatics 22:1238–1240

    Google Scholar 

  147. Mathews DH, Turner DH (2002) Dynalign: an algorithm for finding the secondary structure common to two RNA sequences. J Mol Biol 317:191–203

    Article  CAS  PubMed  Google Scholar 

  148. Fu Y, Sharma G, Mathews DH (2014) Dynalign II: common secondary structure prediction for RNA homologs with domain insertions. Nucleic Acids Res 42:13939–13948

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Will S, Missal K, Hofacker IL, Stadler PF, Backofen R (2007) Inferring non-coding RNA families and classes by means of genome-scale structure-based clustering. PLoS Comput Biol 3:e65

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  150. Will S, Joshi T, Hofacker IL, Stadler PF, Backofen R (2012) LocARNA-P: accurate boundary prediction and improved detection of structured RNAs for genome-wide screens. RNA 18:900–914

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Sankoff D (1985) Simultaneous solution of the RNA folding, alignment and protosequence problems. SIAM J Appl Math 45:810–825

    Article  Google Scholar 

  152. Havgaard JH, Gorodkin J (2014) RNA structural alignments, part I: sankoff-based approaches for structural alignments. Methods Mol Biol 1097:275–290

    Article  PubMed  Google Scholar 

  153. Yao Z, Weinberg Z, Ruzzo WL (2006) CMfinder–a covariance model based RNA motif finding algorithm. Bioinformatics 22(4):445–452

    Article  CAS  PubMed  Google Scholar 

  154. Hofacker IL, Fontana W, Stadler PF, Bonhoeffer LS, Tacker M, Schuster P (1994) Fast folding and comparison of RNA secondary structures. Monatsh Chem 125:167–188

    Article  CAS  Google Scholar 

  155. Bailey TL, Elkan C (1994) Fitting a mixture model by expectation maximization to discover motifs in biopolymers. Proc Int Conf Intell Syst Mol Biol 2:28–36

    CAS  PubMed  Google Scholar 

  156. Ruzzo WL Gorodkin J (2014) De novo discovery of structured ncRNA motifs in genomic sequences. Methods Mol Biol 1097:303–318

    Article  PubMed  Google Scholar 

  157. Puton T, Kozlowski LP, Rother KM, Bujnicki JM (2013) CompaRNA: a server for continuous benchmarking of automated methods for RNA secondary structure prediction. Nucleic Acids Res 41(7):4307–4323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Puton T, Kozlowski LP, Rother KM, Bujnicki JM (2014) CompaRNA: a server for continuous benchmarking of automated methods for RNA secondary structure prediction. Nucleic Acids Res 42(8):5403–5406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Will S, Yu M, Berger B (2013) Structure-based whole-genome realignment reveals many novel noncoding RNAs. Genome Res 23:1018–1027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Torarinsson E, Sawera M, Havgaard JH, Fredholm M, Gorodkin J (2006) Thousands of corresponding human and mouse genomic regions unalignable in primary sequence contain common RNA structure. Genome Res 16:885–889

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Weinberg Z, Barrick JE, Yao Z, Roth A, Kim JN, Gore J, Wang JX, Lee ER, Block KF, Sudarsan N, Neph S, Tompa M, Ruzzo WL, Breaker RR (2007) Identification of 22 candidate structured RNAs in bacteria using the CMfinder comparative genomics pipeline. Nucleic Acids Res 35:4809–4819

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. The ENCODE Project Consortium (2007) Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447:799–816

    Article  PubMed Central  CAS  Google Scholar 

  163. Torarinsson E, Yao Z, Wiklund ED, Bramsen JB, Hansen C, Kjems J, Tommerup N, Ruzzo WL, Gorodkin J (2008) Comparative genomics beyond sequence-based alignments: RNA structures in the ENCODE regions. Genome Res 18:242–251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Ulveling D, Francastel C, Hubé F (2011) When one is better than two: RNA with dual functions. Biochimie 93:633–644

    Article  CAS  PubMed  Google Scholar 

  165. Leygue E (2007) Steroid receptor RNA activator (SRA1): unusual bifaceted gene products with suspected relevance to breast cancer. Nucl Recept Signal 5:e006

    PubMed  PubMed Central  Google Scholar 

  166. Rivas E, Clements J, Eddy SR (2017) A statistical test for conserved RNA structure shows lack of evidence for structure in lncRNAs. Nat Methods 14(1):45–48

    Article  CAS  PubMed  Google Scholar 

  167. Jenny A, Hachet O, Závorszky P, Cyrklaff A, Weston MD, Johnston DS, Erdélyi M, Ephrussi A (2006) A translation-independent role of oskar RNA in early Drosophila oogenesis. Development 133:2827–2833

    Google Scholar 

  168. Weill L, James L, Ulryck N, Chamond N, Herbreteau CH, Ohlmann T, Sargueil B (2010) A new type of IRES within gag coding region recruits three initiation complexes on HIV-2 genomic RNA. Nucleic Acids Res 38:1367–1381

    Article  CAS  PubMed  Google Scholar 

  169. Kumari, P, Sampath K (2015) cncRNAs: bi-functional RNAs with protein coding and non-coding functions. Semin Cell Dev Biol 47–48:40–51

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  170. Neuhaus K, Landstorfer R, Simon S, Schober S, Wright PR, Smith C, Backofen R, Wecko R, Keim DA, Scherer S (2017) Differentiation of ncRNAs from small mRNAs in Escherichia coli O157:H7 EDL933 (EHEC) by combined RNAseq and RIBOseq - ryhB encodes the regulatory RNA RyhB and a peptide, RyhP. BMC Genomics 18(1):216

    Article  PubMed  PubMed Central  Google Scholar 

  171. Pedersen JS, Meyer IM, Forsberg R, Simmonds P, Hein J (2004) A comparative method for finding and folding RNA secondary structures within protein-coding regions. Nucleic Acids Res 32:4925–4936

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Meyer IM, Miklós I (2005) Statistical evidence for conserved, local secondary structure in the coding regions of eukaryotic mRNAs and pre-mRNAs. Nucleic Acids Res 33:6338–6348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Findeiß S, Engelhardt J, Prohaska SP, Stadler PF (2011) Protein-coding structured RNAs: a computational survey of conserved RNA secondary structures overlapping coding regions in drosophilids. Biochimie 93:2019–2023

    Article  PubMed  CAS  Google Scholar 

  174. Stoletzki N (2008) Conflicting selection pressures on synonymous codon use in yeast suggest selection on mRNA secondary structures. BMC Evol Biol 8:224

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  175. Lin MF, Kheradpour P, Washietl S, Parker BJ, Pedersen JS, Kellis M (2011) Locating protein-coding sequences under selection for additional, overlapping functions in 29 mammalian genomes. Genome Res 21:1916–1928

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Roy Stat Soc Ser B 57:289–300

    Google Scholar 

  177. Babak T, Blencowe BJ, Hughes TR (2007) Considerations in the identification of functional RNA structural elements in genomic alignments. BMC Bioinf 8:33

    Article  CAS  Google Scholar 

  178. Anandam P, Torarinsson E, Ruzzo WL (2009) Multiperm: shuffling multiple sequence alignments while approximately preserving dinucleotide frequencies. Bioinformatics 25:668–669

    Article  CAS  PubMed  Google Scholar 

  179. Washietl S, Pedersen JS, Korbel JO, Gruber A, Hackermüller J, Hertel J, Lindemeyer M, Reiche K, Stocsits C, Tanzer A, Ucla C, Wyss C, Antonarakis SE, Denoeud F, Lagarde J, Drenkow J, Kapranov P, Gingeras TR, Guigó R, Snyder M, Gerstein MB, Reymond A, Hofacker IL, Stadler PF (2007) Structured RNAs in the ENCODE selected regions of the human genome. Gen Res 17:852–864

    Article  CAS  Google Scholar 

  180. Rose DR, Hackermüller J, Washietl S, Findeiß S, Reiche K, Hertel J, Stadler PF, Prohaska SJ (2007) Computational RNomics of drosophilids. BMC Genomics 8:406

    Article  PubMed  PubMed Central  Google Scholar 

  181. Theis C, Zirbel CL, Siederdissen CHZ, Anthon C, Hofacker IL, Nielsen H, Gorodkin J (2015) RNA 3D modules in genome-wide predictions of RNA 2D structure. PLoS ONE 10(10):e0139900

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  182. Zhang XH-F, Leslie CS, Chasin LA (2005) Computational searches for splicing signals. Methods 37:292–305

    Article  CAS  PubMed  Google Scholar 

  183. Hiller M, Findeiß S, Lein S, Marz M, Nickel C, Rose D, Schulz C, Backofen R, Prohaska SJ, Reuter G, Stadler PF (2009) Conserved introns reveal novel transcripts in Drosophila melanogaster. Genome Res 19:1289–1300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Rose D, Hiller M, Schutt K, Hackermüller J, Backofen R, Stadler PF (2011) Computational discovery of human coding and non-coding transcripts with conserved splice sites. Bioinformatics 27:1894–1900

    Article  CAS  PubMed  Google Scholar 

  185. Kingsford C, Ayanbule K, Salzberg SL (2007) Rapid, accurate, computational discovery of Rho-independent transcription terminators illuminates their relationship to DNA uptake. Genome Biol 8:R22

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  186. Naville M, Ghuillot-Gaudeffroy A, Marchais A, Gautheret D (2011) ARNold: a web tool for the prediction of Rho-independent transcription terminators. RNA Biol 8:11–13

    Article  CAS  PubMed  Google Scholar 

  187. Pichon C, Felden B (2003) Intergenic sequence inspector: searching and identifying bacterial RNAs. Bioinformatics 19:1707–1709

    Article  CAS  PubMed  Google Scholar 

  188. Livny J, Fogel MA, Davis BM, Waldor MK (2005) sRNAPredict: an integrative computational approach to identify sRNAs in bacterial genomes. Nucleic Acids Res 13:4096–4105

    Article  CAS  Google Scholar 

  189. Pichon C, du Merle L, Caliot M, Trieu-Cuot P, La Bouguénec C (2012) An in silico model for identification of small RNAs in whole bacterial genomes: characterization of antisense RNAs in pathogenic Escherichia coli and Streptococcus agalactiae strains. Nucl Acids Res 40:2846–2861

    Article  CAS  PubMed  Google Scholar 

  190. Arnedo J, Romero-Zaliz R, Zwir I, del Val C (2014) A multiobjective method for robust identification of bacterial small non-coding RNAs. Bioinformatics 30:2875–2882

    Article  CAS  PubMed  Google Scholar 

  191. Marchais A, Naville M, Bohn C, Bouloc P, Gautheret D (2009) Single-pass classification of all noncoding sequences in a bacterial genome using phylogenetic profiles. Genome Res 19:1084–1092

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Ott A, Idali A, Marchais A, Gautheret D (2012) NAPP: the nucleic acid phylogenetic profile database. Nucl Acids Res 40:D205–D209

    Article  CAS  PubMed  Google Scholar 

  193. Weinberg Z, Perreault J, Meyer MM, Breaker RR (2009) Exceptional structured noncoding RNAs revealed by bacterial metagenome analysis. Nature 462(7273):656–659

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  194. Roth A, Weinberg Z, Chen AG, Kim PB, Ames TD, Breaker RR (2014) A widespread self-cleaving ribozyme class is revealed by bioinformatics. Nat Chem Biol 10(1):56–60

    Article  CAS  PubMed  Google Scholar 

  195. Weinberg Z, Kim PB, Chen TH, Li S, Harris KA, Lunse CE, Breaker RR (2015) New classes of self-cleaving ribozymes revealed by comparative genomics analysis. Nat Chem Biol 11(8):606–610

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  196. Pain A, Ott A, Amine H, Rochat T, Bouloc P, Gautheret D (2015) An assessment of bacterial small RNA target prediction programs. RNA Biol 12(5):509–513

    Article  PubMed  PubMed Central  Google Scholar 

  197. Lai D, Meyer IM (2016) A comprehensive comparison of general RNA-RNA interaction prediction methods. Nucleic Acids Res 44(7):e61

    Article  PubMed  CAS  Google Scholar 

  198. Umu SU, Gardner PP (2017) A comprehensive benchmark of RNA-RNA interaction prediction tools for all domains of life. Bioinformatics 33(7):988–996

    PubMed  Google Scholar 

  199. Gerlach W, Giegerich R (2006) GUUGle: a utility for fast exact matching under RNA complementary rules including G-U base pairing. Bioinformatics 22(6):762–764

    Article  CAS  PubMed  Google Scholar 

  200. Tjaden B, Goodwin SS, Opdyke JA, Guillier M, Fu DX, Gottesman S, Storz G (2006) Target prediction for small, noncoding RNAs in bacteria. Nucleic Acids Res 34(9):2791–802

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  201. Wenzel A, Akbasli E, Gorodkin J (2012) RIsearch: fast RNA-RNA interaction search using a simplified nearest-neighbor energy model. Bioinformatics 28(21):2738–2746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  202. Rehmsmeier M, Steffen P, Höchsmann M, Giegerich R (2004) Fast and effective prediction of microRNA/target duplexes. RNA 10(10):1507–1517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  203. Alkan C, Karakoç E, Nadeau JH, Sahinalp SC, Zhang K (2006) RNA-RNA interaction prediction and antisense RNA target search. J Comput Biol 13(2):267–282

    Article  CAS  PubMed  Google Scholar 

  204. Dimitrov RA, Zuker M (2004) Prediction of hybridization and melting for double-stranded nucleic acids. Biophys J 87(1):215–226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  205. Bernhart SH, Tafer H, Muckstein U, Flamm C, Stadler PF, Hofacker IL (2006) Partition function and base pairing probabilities of RNA heterodimers. Algorithms Mol Biol 1(1):3

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  206. Mückstein U, Tafer H, Hackermuller J, Bernhart SH, Stadler PF, Hofacker IL (2006) Thermodynamics of RNA-RNA binding. Bioinformatics 22:1177–1182

    Article  PubMed  CAS  Google Scholar 

  207. Bernhart SH, Mückstein U, Hofacker IL (2011) RNA accessibility in cubic time. Algorithms Mol Biol 6(1):3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  208. Busch A, Richter AS, Backofen R (2008) IntaRNA: efficient prediction of bacterial sRNA targets incorporating target site accessibility and seed regions. Bioinformatics 24(24):2849–2856

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  209. Wright PR, Georg J, Mann M, Sorescu DA, Richter AS, Lott S, Kleinkauf R, Hess WR, Backofen R (2014) CopraRNA and IntaRNA: predicting small RNA targets, networks and interaction domains. Nucleic Acids Res 42(Web Server issue):W119–W123. PRW, JG and MM contributed equally to this work.

    Google Scholar 

  210. Tafer H, Hofacker IL (2008) RNAplex: a fast tool for RNA-RNA interaction search. Bioinformatics 24(22):2657–2663

    Article  CAS  PubMed  Google Scholar 

  211. Chitsaz H, Backofen R, Sahinalp SC (2009) biRNA: fast RNA-RNA binding sites prediction. In: Salzberg S, Warnow T (eds) Proceedings of the 9th workshop on algorithms in bioinformatics (WABI). Lecture notes in computer science, vol. 5724. Springer, Berlin, pp 25–36

    Chapter  Google Scholar 

  212. Salari R, Backofen R, Sahinalp SC (2009) Fast prediction of RNA-RNA interaction. In: Salzberg S, Warnow T (eds) Proceedings of the 9th Workshop on Algorithms in Bioinformatics (WABI). Lecture Notes in Computer Science, vol 5724. Springer, Berlin, pp 261–272

    Chapter  Google Scholar 

  213. Salari R, Backofen R, Sahinalp SC (2010) Fast prediction of RNA-RNA interaction. Algorithms Mol Biol 5:5

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  214. Pervouchine DD (2004) IRIS: intermolecular RNA interaction search. Genome Inform 15(2):92–101

    CAS  PubMed  Google Scholar 

  215. Chitsaz H, Salari R, Sahinalp SC, Backofen R (2009) A partition function algorithm for interacting nucleic acid strands. Bioinformatics 25(12):i365–i373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  216. Huang FWD, Qin J, Reidys CM, Stadler PF (2009) Partition function and base pairing probabilities for RNA-RNA interaction prediction. Bioinformatics 25(20):2646–2654

    Article  CAS  PubMed  Google Scholar 

  217. Seemann SE, Richter AS, Gesell T, Backofen R, Gorodkin J (2011) PETcofold: predicting conserved interactions and structures of two multiple alignments of RNA sequences. Bioinformatics 27(2):211–219

    Article  CAS  PubMed  Google Scholar 

  218. Li AX, Marz M, Qin J, Reidys CM (2011) RNA-RNA interaction prediction based on multiple sequence alignments. Bioinformatics 27(4):456–463

    Article  CAS  PubMed  Google Scholar 

  219. Schattner P, Brooks AN, Lowe TM (2005) The tRNAscan-SE, snoscan and snoGPS web servers for the detection of tRNAs and snoRNAs. Nucl Acid Res 33:W686–W689

    Article  CAS  Google Scholar 

  220. Freyhult E, Edvardsson S, Tamas I, Moulton V, Poole AM (2008) Fisher: a program for the detection of H/ACA snoRNAs using MFE secondary structure prediction and comparative genomics – assessment and update. BMC Res Notes 1:49

    Google Scholar 

  221. Kehr S, Bartschat S, Stadler PF, Tafer H (2011) PLEXY: efficient target prediction for box C/D snoRNAs. Bioinformatics 27:279–280

    Article  CAS  PubMed  Google Scholar 

  222. Tafer H, Kehr S, Hertel J, Stadler PF (2010) RNAsnoop: efficient target prediction for box H/ACA snoRNAs. Bioinformatics 26:610–616

    Article  CAS  PubMed  Google Scholar 

  223. Richter AS, Backofen R (2012) Accessibility and conservation: general features of bacterial small RNA-mRNA interactions? RNA Biol 9(7):954–965

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  224. Wright PR, Richter AS, Papenfort K, Mann M, Vogel J, Hess WR, Backofen R, Georg J (2013) Comparative genomics boosts target prediction for bacterial small RNAs. Proc Natl Acad Sci USA 110(37):E3487–E3496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  225. Alkan F,Wenzel A, Palasca O, Kerpedjiev P, Rudebeck AF, Stadler PF, Hofacker IL,Gorodkin J (2017) RIsearch2: suffix array-based large-scale prediction of RNA-RNA interactions and siRNA off-targets. Nucleic Acids Res. 45: e60

    Google Scholar 

  226. Deigan KE, Li TW, Mathews DH, Weeks KM (2009) Accurate SHAPE-directed RNA structure determination. Proc Natl Acad Sci USA 106:97–102

    Article  CAS  PubMed  Google Scholar 

  227. Zarringhalam K, Meyer MM, Dotu I, Chuang JH, Clote P (2012) Integrating chemical footprinting data into RNA secondary structure prediction. PLoS One 7:e45160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  228. Hajdin CE, Bellaousov S, Huggins W, Leonard CW, Mathews DH, Weeks KM (2013) Accurate SHAPE-directed RNA secondary structure modeling, including pseudoknots. Proc Natl Acad Sci USA 110:5498–5503

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  229. Cordero P, Kladwang W, VanLang CC, Das R (2012) Quantitative dimethyl sulfate mapping for automated RNA secondary structure inference. Biochemistry 51:7037–7039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  230. Kertesz M, Wan Y, Mazor E, Rinn JL, Nutter RC, Chang HY, Segal E (2010) Genome-wide measurement of RNA secondary structure in yeast. Nature 467:103–107

    Article  CAS  PubMed  Google Scholar 

  231. Wan Y, Qu K, Zhang QC, Flynn RA, Manor O, Ouyang Z, Zhang J, Spitale RC, Snyder MP, Segal E, Chang HY (2014) Landscape and variation of RNA secondary structure across the human transcriptome. Nature 505:706–709

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  232. Sükösd Z, Swenson MS, Kjems J, Heitsch CE (2013) Evaluating the accuracy of SHAPE-directed RNA secondary structure predictions. Nucleic Acids Res 41:2807–2816

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  233. Lorenz R, Luntzer D, Hofacker IL, Stadler PF, Wolfinger MT (2016) SHAPE directed RNA folding. Bioinformatics 32:145–147

    CAS  PubMed  Google Scholar 

  234. Lorenz R, Hofacker IL, Stadler PF (2016) RNA folding with hard and soft constraints. Algorithms Mol Biol 11:8

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  235. Ray D, Kazan H, Cook KB, Weirauch MT, Najafabadi HS, Li X, Gueroussov S, Albu M, Zheng H, Yang A, Na H, Irimia M, Matzat LH, Dale RK, Smith SA, Yarosh CA, Kelly SM, Nabet B, Mecenas D, Li W, Laishram RS, Qiao M, Lipshitz HD, Piano F, Corbett AH, Carstens RP, Frey BJ, Anderson RA, Lynch KW, Penalva LO, Lei EP, Fraser AG, Blencowe BJ, Morris QD, Hughes TR (2013) A compendium of RNA-binding motifs for decoding gene regulation. Nature 499:172–177

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  236. Chu C, Qu K, Zhong FL, Artandi SE, Chang HY (2011) Genomic maps of long noncoding RNA occupancy reveal principles of RNA-chromatin interactions. Mol Cell 44:667–678

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  237. Simon MD (2016) Insight into lncRNA biology using hybridization capture analyses. Biochim Biophys Acta 1859:121–127

    Article  CAS  PubMed  Google Scholar 

  238. Birkedal U, Christensen-Dalsgaard M, Krogh N, Sabarinathan R, Gorodkin J, Nielsen H (2015) Profiling of ribose methylations in RNA by high-throughput sequencing. Angew Chem Int Ed Engl 54(2):451–455

    CAS  PubMed  Google Scholar 

  239. Liu N, Pan T (2016) N6-methyladenosine-encoded epitranscriptomics. Nat Struct Mol Biol 23:98–102

    Article  CAS  PubMed  Google Scholar 

  240. Sibbritt T, Shafik A, Clark SJ, Preiss T (2016) Nucleotide-level profiling of m5C RNA methylation. Methods Mol Biol 1358:269–284

    Article  CAS  PubMed  Google Scholar 

  241. Husain B, Hesler S, Cole JL (2015) Regulation of PKR by RNA: formation of active and inactive dimers. Biochemistry 54:6663–6672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  242. Osman F, Jarrous N, Ben-Asouli Y, Kaempfer R (1999) A cis-acting element in the 3’-untranslated region of human TNF-alpha mRNA renders splicing dependent on the activation of protein kinase PKR. Genes Dev 13:3280–3293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  243. Cohen-Chalamish S, Hasson A, Weinberg D, Namer LS, Banai Y, Osman F, Kaempfer R (2009) Dynamic refolding of IFN-gamma mRNA enables it to function as PKR activator and translation template. Nat Chem Biol 5:896–903

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was funded in part by the German Federal Ministry of Education and Research (BMBF; 031A538B) within the German Network for Bioinformatics Infrastructure (de.NBI), the Deutsche Forschungsgemeinschaft (DFG; BA 2168/11-2, BA2168/3-3, and STA 850/19) within the Priority Programme SPP 1738, the Innovation Fund Denmark (0603-00320B, 5163-00010B), The Danish Council for Independent Research (DFF-4005-00443).

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Authors and Affiliations

  1. Bioinformatics Group, Department of Computer Science, University of Freiburg, Georges-Köhler-Allee 106, D-79110 Freiburg, Germany

    Rolf Backofen

  2. Center for non-coding RNA in Technology and Health, Department of Veterinary and Animal Sciences, University of Copenhagen, Grønnegårdsvej 3, DK-1870 Frederiksberg C, Denmark

    Rolf Backofen, Jan Gorodkin, Ivo L. Hofacker & Peter F. Stadler

  3. Institute for Theoretical Chemistry, University of Vienna, Währingerstraße 17, A-1090 Wien, Austria

    Ivo L. Hofacker & Peter F. Stadler

  4. Bioinformatics and Computational Biology Research Group, University of Vienna, Währingerstraße 17, A-1090 Vienna, Austria

    Ivo L. Hofacker

  5. Bioinformatics Group, Department of Computer Science, Interdisciplinary Center for Bioinformatics, University of Leipzig, Härtelstraße 16-18, D-04107 Leipzig, Germany

    Peter F. Stadler

  6. Max Planck Institute for Mathematics in the Sciences, Inselstraße 22, D-04103 Leipzig, Germany

    Peter F. Stadler

  7. Fraunhofer Institute for Cell Therapy and Immunology, Perlickstraße 1, D-04103 Leipzig, Germany

    Peter F. Stadler

  8. Santa Fe Institute, 1399 Hyde Park Rd, Santa Fe, NM 87501, USA

    Peter F. Stadler

Authors
  1. Rolf Backofen
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  2. Jan Gorodkin
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  3. Ivo L. Hofacker
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  4. Peter F. Stadler
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Corresponding author

Correspondence to Peter F. Stadler .

Editor information

Editors and Affiliations

  1. Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, São Paulo, Brazil

    João C. Setubal

  2. Faculty of Technology and Center for Biotechnology (CeBiTec), Bielefeld University, Bielefeld, Germany

    Jens Stoye

  3. Bioinformatics Group, Department of Computer Science, Interdisciplinary Center for Bioinformatics, University of Leipzig, Leipzig, Germany

    Peter F. Stadler

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Backofen, R., Gorodkin, J., Hofacker, I.L., Stadler, P.F. (2018). Comparative RNA Genomics. In: Setubal, J., Stoye, J., Stadler, P. (eds) Comparative Genomics. Methods in Molecular Biology, vol 1704. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7463-4_14

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  • DOI: https://doi.org/10.1007/978-1-4939-7463-4_14

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7461-0

  • Online ISBN: 978-1-4939-7463-4

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