1932

Abstract

Transcriptomics experiments and computational predictions both enable systematic discovery of new functional RNAs. However, many putative noncoding transcripts arise instead from artifacts and biological noise, and current computational prediction methods have high false positive rates. I discuss prospects for improving computational methods for analyzing and identifying functional RNAs, with a focus on detecting signatures of conserved RNA secondary structure. An interesting new front is the application of chemical and enzymatic experiments that probe RNA structure on a transcriptome-wide scale. I review several proposed approaches for incorporating structure probing data into the computational prediction of RNA secondary structure. Using probabilistic inference formalisms, I show how all these approaches can be unified in a well-principled framework, which in turn allows RNA probing data to be easily integrated into a wide range of analyses that depend on RNA secondary structure inference. Such analyses include homology search and genome-wide detection of new structural RNAs.

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2014-05-06
2024-04-19
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Literature Cited

  1. Anandam P, Torarinsson E, Ruzzo WL. 1.  2009. Multiperm: shuffling multiple sequence alignments while approximately preserving dinucleotide frequencies. Bioinformatics 25:668–69 [Google Scholar]
  2. Argaman L, Hershberg R, Vogel J, Bejerano G, Wagner EG. 2.  et al. 2001. Novel small RNA-encoding genes in the intergenic regions of Escherichia coli. Curr. Biol. 11:941–50 [Google Scholar]
  3. Aviran S, Trapnell C, Lucks JB, Mortimer SA, Luo S. 3.  et al. 2011. Modeling and automation of sequencing-based characterization of RNA structure. Proc. Natl. Acad. Sci. USA 108:11069–74 [Google Scholar]
  4. Babak T, Blencowe BJ, Hughes TR. 4.  2005. A systematic search for new mammalian noncoding RNAs indicates little conserved intergenic transcription. BMC Genomics 6:104 [Google Scholar]
  5. Babak T, Blencowe BJ, Hughes TR. 5.  2007. Considerations in the identification of functional RNA structural elements in genomic alignments. BMC Bioinformatics 8:33 [Google Scholar]
  6. Bradley RK, Uzilov AV, Skinner ME, Bendaña YR, Barquist L, Holmes I. 6.  2009. Evolutionary modeling and prediction of non-coding RNAs in Drosophila. PLoS ONE 4:e6478 [Google Scholar]
  7. Brunel C, Romby P, Westhof E, Ehresmann C, Ehresmann B. 7.  1991. Three-dimensional model of Escherichia coli ribosomal 5S RNA as deduced from structure probing in solution and computer modeling. J. Mol. Biol. 221:293–308 [Google Scholar]
  8. Bussotti G, Raineri E, Erb I, Zytnicki M, Wilm A. 8.  et al. 2011. BlastR—fast and accurate database searches for non-coding RNAs. Nucleic Acids Res. 39:6886–95 [Google Scholar]
  9. Clark MB, Amaral PP, Schlesinger FJ, Dinger ME, Taft RJ. 9.  et al. 2011. The reality of pervasive transcription. PLoS Biol 9:e1000625 [Google Scholar]
  10. Cordero P, Kladwang W, VanLang CC, Das R. 10.  2012. Quantitative dimethyl sulfate mapping for automated RNA secondary structure inference. Biochemistry 51:7037–39 [Google Scholar]
  11. Coventry A, Kleitman DJ, Berger B. 11.  2004. MSARI: multiple sequence alignments for statistical detection of RNA secondary structure. Proc. Natl. Acad. Sci. USA 101:12102–7 [Google Scholar]
  12. Deigan KE, Li TW, Mathews DH, Weeks KM. 12.  2009. Accurate SHAPE-directed RNA structure determination. Proc. Natl. Acad. Sci. USA 106:97–102Pioneering paper on SHAPE-directed RNA secondary structure prediction. [Google Scholar]
  13. di Bernardo D, Down T, Hubbard T. 13.  2003. ddbRNA: detection of conserved secondary structures in multiple alignments. Bioinformatics 19:1606–11 [Google Scholar]
  14. Ding Y, Lawrence CE. 14.  2003. A statistical sampling algorithm for RNA secondary structure prediction. Nucleic Acids Res. 31:7280–301 [Google Scholar]
  15. Dinger ME, Amaral PP, Mercer TR, Mattick JS. 15.  2009. Pervasive transcription of the eukaryotic genome: functional indices and conceptual implications. Brief. Funct. Genomic. Proteomic. 8:407–23 [Google Scholar]
  16. Djebali S, Davis CA, Merkel A, Dobin A, Lassmann T. 16.  et al. 2012. Landscape of transcription in human cells. Nature 489:101–8 [Google Scholar]
  17. Eddy SR. 17.  2013. The ENCODE project: mistakes overshadowing a success. Curr. Biol. 23:R259–261 [Google Scholar]
  18. Eddy SR, Durbin R. 18.  1994. RNA sequence analysis using covariance models. Nucleic Acids Res. 22:2079–88 [Google Scholar]
  19. Ehresmann C, Baudin F, Mougel M, Romby P, Ebel JP, Ehresmann B. 19.  1987. Probing the structure of RNAs in solution. Nucleic Acids Res. 15:9109–28 [Google Scholar]
  20. ENCODE Project Consortium 2012. An integrated encyclopedia of DNA elements in the human genome. Nature 489:57–74 [Google Scholar]
  21. Evans M, Hastings N, Peacock B. 21.  2000. Statistical Distributions New York: Wiley, 3rd ed..
  22. Freier SM, Kierzek R, Jaeger JA, Sugimoto N, Caruthers MH. 22.  et al. 1986. Improved free-energy parameters for predictions of RNA duplex stability. Proc. Natl. Acad. Sci. USA 83:9373–77 [Google Scholar]
  23. Gesell T, von Haeseler A. 23.  2006. In silico sequence evolution with site-specific interactions along phylogenetic trees. Bioinformatics 22:716–22 [Google Scholar]
  24. Gesell T, Washietl S. 24.  2008. Dinucleotide controlled null models for comparative RNA gene prediction. BMC Bioinformatics 9:248 [Google Scholar]
  25. Gottesman S, Storz G. 25.  2011. Bacterial small RNA regulators: versatile roles and rapidly evolving variations. Cold Spring Harb. Perspect. Biol. 3:a003798 [Google Scholar]
  26. Gruber AR, Bernhart SH, Hofacker IL, Washietl S. 26.  2008. Strategies for measuring evolutionary conservation of RNA secondary structures. BMC Bioinformatics 9:122 [Google Scholar]
  27. Gruber AR, Findeiß S, Washietl S, Hofacker IL, Stadler PF. 27.  2010. RNAz 2.0: improved noncoding RNA detection. Pac. Symp. Biocomput. 15:69–79 [Google Scholar]
  28. Guttman M, Rinn JL. 28.  2012. Modular regulatory principles of large non-coding RNAs. Nature 482:339–46 [Google Scholar]
  29. Hajdin CE, Bellaousov S, Huggins W, Leonard CW, Mathews DH, Weeks KM. 29.  2013. Accurate SHAPE-directed RNA secondary structure modeling, including pseudoknots. Proc. Natl. Acad. Sci. USA 110:5498–503 [Google Scholar]
  30. Hangauer MJ, Vaughn IW, McManus MT. 30.  2013. Pervasive transcription of the human genome produces thousands of previously unidentified long intergenic noncoding RNAs. PLoS Genet. 9:e1003569Comprehensive survey and meta-analysis of human transcriptomic data from 127 different RNA-seq libraries. [Google Scholar]
  31. Hobbs EC, Fontaine F, Yin X, Storz G. 31.  2011. An expanding universe of small proteins. Curr. Opin. Microbiol. 14:167–73 [Google Scholar]
  32. Hogan DJ, Riordan DP, Gerber AP, Herschlag D, Brown PO. 32.  2008. Diverse RNA-binding proteins interact with functionally related sets of RNAs, suggesting an extensive regulatory system. PLoS Biol. 6:e255 [Google Scholar]
  33. Inoue T, Cech TR. 33.  1985. Secondary structure of the circular form of the Tetrahymena rRNA intervening sequence: a technique for RNA structure analysis using chemical probes and reverse transcriptase. Proc. Natl. Acad. Sci. USA 82:648–52 [Google Scholar]
  34. Kageyama Y, Kondo T, Hashimoto Y. 34.  2011. Coding versus non-coding: translatability of short ORFs found in putative non-coding transcripts. Biochimie 93:1981–86 [Google Scholar]
  35. Kapranov P, Cawley SE, Drenkow J, Bekiranov S, Strausberg RL. 35.  et al. 2002. Large-scale transcriptional activity in chromosomes 21 and 22. Science 296:916–19 [Google Scholar]
  36. Kapranov P, Laurent GS. 36.  2012. Dark matter RNA: existence, function, and controversy. Front. Genet. 3:60 [Google Scholar]
  37. Kertesz M, Wan Y, Mazor E, Rinn JL, Nutter RC. 37.  et al. 2010. Genome-wide measurement of RNA secondary structure in yeast. Nature 467:103–7Describes parallel analysis of RNA structure (PARS), a transcriptome-wide application of RNA structure probing. [Google Scholar]
  38. Kladwang W, VanLang CC, Cordero P, Das R. 38.  2011. A two-dimensional mutate-and-map strategy for non-coding RNA structure. Nat. Chem. 3:954–62 [Google Scholar]
  39. Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. 39.  2001. Identification of novel genes coding for small expressed RNAs. Science 294:853–58 [Google Scholar]
  40. Lau NC, Lim LP, Weinstein EG, Bartel DP. 40.  2001. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science 294:858–62 [Google Scholar]
  41. Le SY, Chen JH, Currey KM, Maizel JV. 41.  1988. A program for predicting significant RNA secondary structures. Comput. Applic. Biosci. 4:153–59 [Google Scholar]
  42. Lécuyer E, Yoshida H, Parthasarathy N, Alm C, Babak T. 42.  et al. 2007. Global analysis of mRNA localization reveals a prominent role in organizing cellular architecture and function. Cell 131:174–87 [Google Scholar]
  43. Li F, Zheng Q, Ryvkin P, Dragomir I, Desai Y. 43.  et al. 2012. Global analysis of RNA secondary structure in two metazoans. Cell Rep. 1:69–82 [Google Scholar]
  44. Li S, Breaker RR. 44.  2013. Eukaryotic TPP riboswitch regulation of alternative splicing involving long-distance base pairing. Nucleic Acids Res. 41:3022–31 [Google Scholar]
  45. Lin MF, Jungreis I, Kellis M. 45.  2011. PhyloCSF: a comparative genomics method to distinguish protein coding and non-coding regions. Bioinformatics 27:i275–82 [Google Scholar]
  46. Low JT, Weeks KM. 46.  2010. SHAPE-directed RNA secondary structure prediction. Methods 52:150–58 [Google Scholar]
  47. Lu ZJ, Turner DH, Mathews DH. 47.  2006. A set of nearest neighbor parameters for predicting the enthalpy change of RNA secondary structure formation. Nucleic Acids Res. 34:4912–24 [Google Scholar]
  48. Lucks JB, Mortimer SA, Trapnell C, Luo S, Aviran S. 48.  et al. 2011. Multiplexed RNA structure characterization with selective 2′-hydroxyl acylation analyzed by primer extension sequencing (SHAPE-seq). Proc. Natl. Acad. Sci. USA 108:11063–68 [Google Scholar]
  49. Macke TJ, Ecker DJ, Gutell RR, Gautheret D, Case DA, Sampath R. 49.  2001. RNAMotif, an RNA secondary structure definition and search algorithm. Nucleic Acids Res 29:4724–35 [Google Scholar]
  50. Maenner S, Blaud M, Fouillen L, Savoye A, Marchand V. 50.  et al. 2010. 2-D structure of the A region of Xist RNA and its implication for PRC2 association. PLoS Biol. 8:e1000276 [Google Scholar]
  51. Matera AG, Terns RM, Terns MP. 51.  2007. Non-coding RNAs: lessons from the small nuclear and small nucleolar RNAs. Nat. Rev. Mol. Cell Biol. 8:209–20 [Google Scholar]
  52. Mathews DH, Disney DH, Childs MD, Schroeder JL, Zuker M, Turner DH. 52.  2004. Incorporating chemical modification constraints into a dynamic programming algorithm for prediction of RNA secondary structure. Proc. Natl. Acad. Sci. USA 101:7287–92 [Google Scholar]
  53. Mathews DH, Sabina J, Zuker M, Turner DH. 53.  1999. Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structure. J. Mol. Biol. 288:911–40 [Google Scholar]
  54. Mathews DH, Turner DH. 54.  2002. Dynalign: an algorithm for finding the secondary structure common to two RNA sequences. J. Mol. Biol. 317:191–203 [Google Scholar]
  55. Mazo A, Hodgson JW, Petruk S, Sedkov Y, Brock HW. 55.  2007. Transcriptional interference: an unexpected layer of complexity in gene regulation. J. Cell Sci. 120:2755–61 [Google Scholar]
  56. McCaskill JS. 56.  1990. The equilibrium partition function and base pair binding probabilities for RNA secondary structure. Biopolymers 29:1105–19 [Google Scholar]
  57. McGinnis JL, Dunkle JA, Cate JH, Weeks KM. 57.  2012. The mechanisms of RNA SHAPE chemistry. J. Am. Chem. Soc. 134:6617–24 [Google Scholar]
  58. Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J. 58.  et al. 2013. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 495:333–38 [Google Scholar]
  59. Merino EJ, Wilkinson KA, Coughlan JL, Weeks KM. 59.  2005. RNA structure analysis at single nucleotide resolution by selective 2′-hydroxyl acylation and primer extension (SHAPE). J. Am. Chem. Soc. 127:4223–31 [Google Scholar]
  60. Mitra S, Shcherbakova IV, Altman RB, Brenowitz M, Laederach A. 60.  2008. High-throughput single-nucleotide structural mapping by capillary automated footprinting analysis. Nucleic Acids Res. 36:e63 [Google Scholar]
  61. Moazed D, Stern S, Noller HF. 61.  1986. Rapid chemical probing of conformation in 16S ribosomal RNA and 30S ribosomal subunits using primer extension. J. Mol. Biol. 187:399–416 [Google Scholar]
  62. Mortazavi A, Williams BA, McCue K, Schaeffer L, Wold B. 62.  2008. Mapping and quantifying mammalian transcriptomes by RNA-seq. Nat. Methods 5:621–28 [Google Scholar]
  63. Mortimer SA, Weeks KM. 63.  2007. A fast-acting reagent for accurate analysis of RNA secondary and tertiary structure by SHAPE chemistry. J. Am. Chem. Soc. 129:4144–45 [Google Scholar]
  64. Nawrocki EP, Eddy SR. 64.  2013. Infernal 1.1: 100-fold faster RNA homology searches. Bioinformatics 29:2933–35 [Google Scholar]
  65. Nordström KJ, Mirza MA, Almén MS, Gloriam DE, Fredriksson R, Schiöth HB. 65.  2009. Critical evaluation of the FANTOM3 non-coding RNA transcripts. Genomics 94:169–76A thorough reanalysis of FANTOM3's so-called noncoding RNAs, showing that they were contaminated with several artifacts. [Google Scholar]
  66. Novikova IV, Hennelly SP, Sanbonmatsu KY. 66.  2012. Structural architecture of the human long non-coding RNA, steroid receptor RNA activator. Nucleic Acids Res. 40:5034–51 [Google Scholar]
  67. Nussinov R, Pieczenik G, Griggs JR, Kleitman DJ. 67.  1978. Algorithms for loop matchings. SIAM J. Appl. Math. 35:68–82 [Google Scholar]
  68. Okazaki Y, Furuno M, Kasukawa T, Adachi J, Bono H. 68.  et al. 2002. Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs. Nature 420:563–73 [Google Scholar]
  69. Ouyang Z, Snyder MP, Chang HY. 69.  2013. SeqFold: genome-scale reconstruction of RNA secondary structure integrating high-throughput sequencing data. Genome Res. 23:377–87 [Google Scholar]
  70. Pang PS, Elazar M, Pham EA, Glenn JS. 70.  2011. Simplified RNA secondary structure mapping by automation of SHAPE data analysis. Nucleic Acids Res. 39:e151 [Google Scholar]
  71. Parker BJ, Moltke I, Roth A, Washietl S, Wen J. 71.  et al. 2011. New families of human regulatory RNA structures identified by comparative analysis of vertebrate genomes. Genome Res. 21:1929–43 [Google Scholar]
  72. Pedersen JS, Bejerano G, Siepel A, Rosenbloom K, Lindblad-Toh K. 72.  et al. 2006. Identification and classification of conserved RNA secondary structures in the human genome. PLoS Comput. Biol. 2:e33 [Google Scholar]
  73. Peluso P, Herschlag D, Nock S, Freymann DM, Johnson AE, Walter P. 73.  2000. Role of 4.5S RNA in assembly of the bacterial signal recognition particle with its receptor. Science 288:1640–43 [Google Scholar]
  74. Perreault J, Weinberg Z, Roth A, Popescu O, Chartrand P. 74.  et al. 2011. Identification of hammerhead ribozymes in all domains of life reveals novel structural variations. PLoS Comput. Biol. 7:e1002031 [Google Scholar]
  75. Pickrell JK, Pai AA, Gilad Y, Pritchard JK. 75.  2010. Noisy splicing drives mRNA isoform diversity in human cells. PLoS Genet. 6:e1001236 [Google Scholar]
  76. Ponting CP, Belgard TG. 76.  2010. Transcribed dark matter: meaning or myth?. Hum. Mol. Genet. 19:R162–68 [Google Scholar]
  77. Quarrier S, Martin JS, Davis-Neulander L, Beauregard A, Laederach A. 77.  2010. Evaluation of the information content of RNA structure mapping data for secondary structure prediction. RNA 16:1108–17 [Google Scholar]
  78. Rabani M, Kertesz M, Segal E. 78.  2008. Computational prediction of RNA structural motifs involved in posttranscriptional regulatory processes. Proc. Natl. Acad. Sci. USA 105:14885–90 [Google Scholar]
  79. Rabani M, Kertesz M, Segal E. 79.  2011. Computational prediction of RNA structural motifs involved in post-transcriptional regulatory processes. Methods Mol. Biol. 714:467–79 [Google Scholar]
  80. Ray D, Kazan H, Cook KB, Weirauch MT, Najafabadi HS. 80.  et al. 2013. A compendium of RNA-binding motifs for decoding gene regulation. Nature 499:172–77 [Google Scholar]
  81. Reichow SL, Hamma T, Ferré-D'Amaré AR, Varani G. 81.  2007. The structure and function of small nucleolar ribonucleoproteins. Nucleic Acids Res. 35:1452–64 [Google Scholar]
  82. Rinn JL, Chang HY. 82.  2012. Genome regulation by long noncoding RNAs. Annu. Rev. Biochem. 81:145–66 [Google Scholar]
  83. Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X. 83.  et al. 2007. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 129:1311–23 [Google Scholar]
  84. Riordan DP, Herschlag D, Brown PO. 84.  2011. Identification of RNA recognition elements in the Saccharomyces cerevisiae transcriptome. Nucleic Acids Res. 39:1501–9 [Google Scholar]
  85. Rivas E, Eddy SR. 85.  2000. Secondary structure alone is generally not statistically significant for the detection of noncoding RNAs. Bioinformatics 6:583–605 [Google Scholar]
  86. Rivas E, Eddy SR. 86.  2001. Noncoding RNA gene detection using comparative sequence analysis. BMC Bioinformatics 2:8 [Google Scholar]
  87. Rivas E, Klein RJ, Jones TA, Eddy SR. 87.  2001. Computational identification of noncoding RNAs in E. coli by comparative genomics. Curr. Biol. 11:1369–73 [Google Scholar]
  88. Rivas E, Lang R, Eddy SR. 88.  2012. A range of complex probabilistic models for RNA secondary structure prediction that include the nearest neighbor model and more. RNA 18:193–212 [Google Scholar]
  89. Sakakibara Y, Brown M, Hughey R, Mian IS, Sjölander K. 89.  et al. 1994. Stochastic context-free grammars for tRNA modeling. Nucleic Acids Res. 22:5112–20 [Google Scholar]
  90. Salehi-Ashtiani K, Lupták A, Litovchick A, Szostak JW. 90.  2006. A genomewide search for ribozymes reveals an HDV-like sequence in the human CPEB3 gene. Science 313:1788–92 [Google Scholar]
  91. Seemann SE, Sunkin SM, Hawrylycz MJ, Ruzzo WL, Gorodkin J. 91.  2012. Transcripts with in silico predicted RNA structure are enriched everywhere in the mouse brain. BMC Genomics 13:214 [Google Scholar]
  92. Serganov A, Nudler E. 92.  2013. A decade of riboswitches. Cell 152:17–24 [Google Scholar]
  93. Silverman IM, Li F, Gregory BD. 93.  2013. Genomic era analyses of RNA secondary structure and RNA-binding proteins reveal their significance to post-transcriptional regulation in plants. Plant Sci. 205:55–62 [Google Scholar]
  94. Smith CM, Steitz JA. 94.  1998. Classification of gas5 as a multi-small-nucleolar-RNA (snoRNA) host gene and a member of the 5′-terminal oligopyrimidine gene family reveals common features of snoRNA host genes. Mol. Cell. Biol. 18:6897–909 [Google Scholar]
  95. Smith MA, Gesell T, Stadler PF, Mattick JS. 95.  2013. Widespread purifying selection on RNA structure in mammals. Nucleic Acids Res. 41:8220–36The most recent human genome-wide computational screen for conserved RNA structure detection. [Google Scholar]
  96. Spitale RC, Crisalli P, Flynn RA, Torre EA, Kool ET, Chang HY. 96.  2013. RNA SHAPE analysis in living cells. Nat. Chem. Biol. 9:18–20 [Google Scholar]
  97. Storz G, Vogel J, Wassarman KM. 97.  2011. Regulation by small RNAs in bacteria: expanding frontiers. Mol. Cell. 43:880–91 [Google Scholar]
  98. Stricklin SL. 98.  2006. Noncoding RNA Genes in Caenorhabditis elegans. PhD Thesis, Wash. Univ. Sch. Med. [Google Scholar]
  99. Struhl K. 99.  2007. Transcriptional noise and the fidelity of initiation by RNA polymerase II. Nat. Struct. Mol. Biol. 14:103–5 [Google Scholar]
  100. Sükösd Z, Knudsen B, Kjems J, Pedersen CN. 100.  2012. PPfold 3.0: fast RNA secondary structure prediction using phylogeny and auxiliary data. Bioinformatics 28:2691–92 [Google Scholar]
  101. Sükösd Z, Swenson MS, Kjems J, Heitsch CE. 101.  2013. Evaluating the accuracy of SHAPE-directed RNA secondary structure predictions. Nucleic Acids Res. 41:2807–16One of few places where empirical distributions for SHAPE data have been shown. [Google Scholar]
  102. Torarinsson E, Sawera M, Havgaard JH, Fredholm M, Gorodkin J. 102.  2006. Thousands of corresponding human and mouse genomic regions unalignable in primary sequence contain common RNA structure. Genome Res. 16:885–89 [Google Scholar]
  103. Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK. 103.  et al. 2010. Long noncoding RNA as modular scaffold of histone modification complexes. Science 329:689–93 [Google Scholar]
  104. Tycowski KT, Shu MD, Steitz JA. 104.  1996. A mammalian gene with introns instead of exons generating stable RNA products. Nature 379:464–66 [Google Scholar]
  105. Underwood JG, Uzilov AV, Katzman S, Onodera CS, Mainzer JE. 105.  et al. 2010. FragSeq: transcriptome-wide RNA structure probing using high-throughput sequencing. Nat. Methods 7:995–1001Describes FragSeq, a transcriptome-wide application of RNA structure probing. [Google Scholar]
  106. Uzilov AV, Keegan JM, Mathews DH. 106.  2006. Detection of non-coding RNAs on the basis of predicted secondary structure formation free energy change. BMC Bioinformatics 7:173 [Google Scholar]
  107. van Bakel H, Hughes TR. 107.  2009. Establishing legitimacy and function in the new transcriptome. Brief. Funct. Genomic. Proteomic. 8:424–36 [Google Scholar]
  108. van Bakel H, Hughes TR. 108.  2010. Most “dark matter” transcripts are associated with known genes. PLoS Biol. 8:e1000371 [Google Scholar]
  109. van Bakel H, Nislow C, Blencowe BJ, Hughes TR. 109.  2011. Response to “the reality of pervasive transcription”. PLoS Biol. 9:e1001102 [Google Scholar]
  110. Vasa SM, Guex N, Wilkinson KA, Weeks KM, Giddings MC. 110.  2008. ShapeFinder: a software system for high-throughput quantitative analysis of nucleic acid reactivity information resolved by capillary electrophoresis. RNA 14:1979–90 [Google Scholar]
  111. Wan Y, Qu K, Ouyang Z, Chang HY. 111.  2013. Genome-wide mapping of RNA structure using nuclease digestion and high-throughput sequencing. Nat. Protoc. 8:849–69 [Google Scholar]
  112. Washietl S, Findeiss S, Müller SA, Kalkhof S, von Bergen M. 112.  et al. 2011. RNAcode: robust discrimination of coding and noncoding regions in comparative sequence data. RNA 17:578–94 [Google Scholar]
  113. Washietl S, Hofacker IL. 113.  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 [Google Scholar]
  114. Washietl S, Hofacker IL, Lukasser M, Hüttenhofer A, Stadler PF. 114.  2005. Mapping of conserved RNA secondary structures predicts thousands of functional noncoding RNAs in the human genome. Nat. Biotechnol. 23:1383–90 [Google Scholar]
  115. Washietl S, Hofacker IL, Stadler PF. 115.  2005. Fast and reliable prediction of noncoding RNAs. Proc. Natl. Acad. Sci. USA 102:2454–59 [Google Scholar]
  116. Washietl S, Hofacker IL, Stadler PF, Kellis M. 116.  2012. RNA folding with soft constraints: reconciliation of probing data and thermodynamic secondary structure prediction. Nucleic Acids Res. 40:4261–72A conceptually different approach for SHAPE-directed structure prediction, focused on ensemble calculations. [Google Scholar]
  117. Washietl S, Pedersen JS, Korbel JO, Stocsits C, Gruber AR. 117.  et al. 2007. Structured RNAs in the ENCODE selected regions of the human genome. Genome Res. 17:852–64 [Google Scholar]
  118. Wassarman KM, Repoila F, Rosenow C, Storz G, Gottesman S. 118.  2001. Identification of novel small RNAs using comparative genomics and microarrays. Genes Dev. 15:1637–51 [Google Scholar]
  119. Watts JM, Dang KK, Gorelick RJ, Leonard CW, Bess JW Jr. 119.  et al. 2009. Architecture and secondary structure of an entire HIV-1 RNA genome. Nature 460:711–16 [Google Scholar]
  120. Wei D, Alpert LV, Lawrence CE. 120.  2011. RNAG: a new Gibbs sampler for predicting RNA secondary structure for unaligned sequences. Bioinformatics 27:2486–93 [Google Scholar]
  121. Westholm JO, Lai EC. 121.  2011. Mirtrons: microRNA biogenesis via splicing. Biochimie 93:1897–904 [Google Scholar]
  122. Will S, Siebauer MF, Heyne S, Engelhardt J, Stadler PF. 122.  et al. 2013. LocARNAscan: incorporating thermodynamic stability in sequence and structure-based RNA homology search. Algorithms Mol. Biol. 8:14 [Google Scholar]
  123. Will S, Yu M, Berger B. 123.  2013. Structure-based whole-genome realignment reveals many novel noncoding RNAs. Genome Res. 23:1018–27 [Google Scholar]
  124. Wilm A, Higgins DG, Notredame C. 124.  2008. R-Coffee: a method for multiple alignment of non-coding RNA. Nucleic Acids Res. 36:e52 [Google Scholar]
  125. Wilusz JE, Freier SM, Spector DL. 125.  2008. 3′ end processing of a long nuclear-retained noncoding RNA yields a tRNA-like cytoplasmic RNA. Cell 135:919–32 [Google Scholar]
  126. Wilusz JE, Spector DL. 126.  2010. An unexpected ending: noncanonical 3′ end processing mechanisms. RNA 16:259–66 [Google Scholar]
  127. Workman C, Krogh A. 127.  1999. No evidence that mRNAs have lower folding free energies than random sequences with the same dinucleotide distribution. Nucleic Acids Res. 27:4816–22 [Google Scholar]
  128. Xia T, SantaLucia J Jr, Burkard ME, Kierzek R, Schroeder SJ. 128.  et al. 1998. Thermodynamic parameters for an expanded nearest-neighbor model for formation of RNA duplexes with Watson–Crick base pairs. Biochemistry 37:14719–35 [Google Scholar]
  129. Yao Z, Weinberg Z, Ruzzo WL. 129.  2006. CMfinder—a covariance model based RNA motif finding algorithm. Bioinformatics 22:445–52 [Google Scholar]
  130. Zappulla DC, Cech TR. 130.  2004. Yeast telomerase RNA: a flexible scaffold for protein subunits. Proc. Natl. Acad. Sci. USA 101:10024–29 [Google Scholar]
  131. Zarringhalam K, Meyer MM, Dotu I, Chuang JH, Clote P. 131.  2012. Integrating chemical footprinting data into RNA secondary structure prediction. PLoS ONE 7:e45160An approach for SHAPE-directed secondary structure prediction that contrasts to Reference 12. [Google Scholar]
  132. Zhang Z, Huang S, Wang J, Zhang X, de Villena FPM. 132.  et al. 2013. GeneScissors: a comprehensive approach to detecting and correcting spurious transcriptome inference owing to RNA-seq reads misalignment. Bioinformatics 29:i291–99 [Google Scholar]
  133. Zheng Q, Ryvkin P, Li F, Dragomir I, Valladares O. 133.  et al. 2010. Genome-wide double-stranded RNA sequencing reveals the functional significance of base-paired RNAs in Arabidopsis. PLoS Genet. 6:e1001141 [Google Scholar]
  134. Zuker M. 134.  1989. On finding all suboptimal foldings of an RNA molecule. Science 244:48–52 [Google Scholar]
  135. Zuker M, Stiegler P. 135.  1981. Optimal computer folding of large RNA sequences using thermodynamics and auxiliary information. Nucleic Acids Res. 9:133–48 [Google Scholar]
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