RNA transcripts fold into secondary structures via intricate patterns of base pairing. These secondary structures impart catalytic, ligand binding, and scaffolding functions to a wide array of RNAs, forming a critical node of biological regulation. Among their many functions, RNA structural elements modulate epigenetic marks, alter mRNA stability and translation, regulate alternative splicing, transduce signals, and scaffold large macromolecular complexes. Thus, the study of RNA secondary structure is critical to understanding the function and regulation of RNA transcripts. Here, we review the origins, form, and function of RNA secondary structure, focusing on plants. We then provide an overview of methods for probing secondary structure, from physical methods such as X-ray crystallography and nuclear magnetic resonance (NMR) imaging to chemical and nuclease probing methods. Combining these latter methods with high-throughput sequencing has enabled them to scale across whole transcriptomes, yielding tremendous new insights into the form and function of RNA secondary structure.


Article metrics loading...

Loading full text...

Full text loading...


Literature Cited

  1. Andersen J, Delihas N, Hanas JS, Wu CW. 1.  1984. 5S RNA structure and interaction with transcription factor A. 1. Ribonuclease probe of the structure of 5S RNA from Xenopus laevis oocytes. Biochemistry 23:5752–59 [Google Scholar]
  2. Antal M, Boros E, Solymosy F, Kiss T. 2.  2002. Analysis of the structure of human telomerase RNA in vivo. Nucleic Acids Res. 30:912–20 [Google Scholar]
  3. Ares M, Igel AH. 3.  1990. Lethal and temperature-sensitive mutations and their suppressors identify an essential structural element in U2 small nuclear RNA. Genes Dev. 4:2132–45 [Google Scholar]
  4. Backe PH, Messias AC, Ravelli RBG, Sattler M, Cusack S. 4.  2005. X-ray crystallographic and NMR studies of the third KH domain of hnRNP K in complex with single-stranded nucleic acids. Structure 13:1055–67 [Google Scholar]
  5. Bai Y, Dai X, Harrison AP, Chen M. 5.  2015. RNA regulatory networks in animals and plants: a long noncoding RNA perspective. Brief. Funct. Genom. 14:91–101 [Google Scholar]
  6. Bartel DP, Unrau PJ. 6.  1999. Constructing an RNA world. Trends Cell Biol. 9:M9–13 [Google Scholar]
  7. Bhaskaran H, Rodriguez-Hernandez A, Perona JJ. 7.  2012. Kinetics of tRNA folding monitored by aminoacylation. RNA 18:569–80 [Google Scholar]
  8. Bhattacharya D, Medlin L. 8.  1995. The phylogeny of plastids: a review based on comparisons of small-subunit ribosomal RNA coding regions. J. Phycol. 31:489–98 [Google Scholar]
  9. Blad H, Reiter NJ, Abildgaard F, Markley JL, Butcher SE. 9.  2005. Dynamics and metal ion binding in the U6 RNA intramolecular stem-loop as analyzed by NMR. J. Mol. Biol. 353:540–55 [Google Scholar]
  10. Bocobza SE, Adato A, Mandel T, Shapira M, Nudler E, Aharoni A. 10.  2007. Riboswitch-dependent gene regulation and its evolution in the plant kingdom. Genes Dev. 21:2874–79 [Google Scholar]
  11. Bocobza SE, Aharoni A. 11.  2014. Small molecules that interact with RNA: riboswitch-based gene control and its involvement in metabolic regulation in plants and algae. Plant J. 79:693–703 [Google Scholar]
  12. Bothe JR, Nikolova EN, Eichhorn CD, Chugh J, Hansen AL, Al-Hashimi HM. 12.  2011. Characterizing RNA dynamics at atomic resolution using solution-state NMR spectroscopy. Nat. Methods 8:919–31 [Google Scholar]
  13. Boza G, Szilágyi A, Kun Á, Santos M, Szathmáry E. 13.  2014. Evolution of the division of labor between genes and enzymes in the RNA world. PLOS Comput. Biol. 10:e1003936 [Google Scholar]
  14. Braddock DT, Louis JM, Baber JL, Levens D, Clore GM. 14.  2002. Structure and dynamics of KH domains from FBP bound to single-stranded DNA. Nature 415:1051–56 [Google Scholar]
  15. Brown GG, Colas des Francs-Small C, Ostersetzer-Biran O. 15.  2014. Group II intron splicing factors in plant mitochondria. Front. Plant Sci. 5:35 [Google Scholar]
  16. Bullock SL, Ringel I, Ish-Horowicz D, Lukavsky PJ. 16.  2010. A′-form RNA helices are required for cytoplasmic mRNA transport in Drosophila. Nat. Struct. Mol. Biol. 17:703–9 [Google Scholar]
  17. Buratti E, Baralle FE. 17.  2004. Influence of RNA secondary structure on the pre-mRNA splicing process. Mol. Cell. Biol. 24:10505–14 [Google Scholar]
  18. Buzayan JM, Gerlach WL, Bruening G. 18.  1986. Non-enzymatic cleavage and ligation of RNAs complementary to a plant virus satellite RNA. Nature 323:349–53 [Google Scholar]
  19. Carthew RW, Sontheimer EJ. 19.  2009. Origins and mechanisms of miRNAs and siRNAs. Cell 136:642–55 [Google Scholar]
  20. Castiglioni P, Warner D, Bensen RJ, Anstrom DC, Harrison J. 20.  et al. 2008. Bacterial RNA chaperones confer abiotic stress tolerance in plants and improved grain yield in maize under water-limited conditions. Plant Physiol. 147:446–55 [Google Scholar]
  21. Chaikam V, Karlson D. 21.  2008. Functional characterization of two cold shock domain proteins from Oryza sativa. Plant Cell Environ. 31:995–1006 [Google Scholar]
  22. Chang SH, RajBhandary UL. 22.  1968. Studies on polynucleotides. LXXXI. Yeast phenylalanine transfer ribonucleic acid: partial digestion with pancreatic ribonuclease. J. Biol. Chem. 243:592–97 [Google Scholar]
  23. Chapman EJ, Carrington JC. 23.  2007. Specialization and evolution of endogenous small RNA pathways. Nat. Rev. Genet. 8:884–96 [Google Scholar]
  24. Chaulk SG, Smith-Frieday MN, Arthur DC, Culham DE, Edwards RA. 24.  et al. 2011. ProQ is an RNA chaperone that controls ProP levels in Escherichia coli. Biochemistry 50:3095–106 [Google Scholar]
  25. Collins K. 25.  2008. Physiological assembly and activity of human telomerase complexes. Mech. Ageing Dev. 129:91–98 [Google Scholar]
  26. Daniele Salvi GB. 26.  2010. The analysis of rRNA sequence-structure in phylogenetics: an application to the family Pectinidae (Mollusca: Bivalvia). Mol. Phylogenet. Evol. 56:1059–67 [Google Scholar]
  27. Demeshkina N, Jenner L, Yusupova G, Yusupov M. 27.  2010. Interactions of the ribosome with mRNA and tRNA. Curr. Opin. Struct. Biol. 20:325–32 [Google Scholar]
  28. Desai NA, Shankar V. 28.  2003. Single-strand-specific nucleases. FEMS Microbiol. Rev. 26:457–91 [Google Scholar]
  29. Ding J, Hayashi MK, Zhang Y, Manche L, Krainer AR, Xu R-M. 29.  1999. Crystal structure of the two-RRM domain of hnRNP A1 (UP1) complexed with single-stranded telomeric DNA. Genes Dev. 13:1102–15 [Google Scholar]
  30. Ding Y, Tang Y, Kwok CK, Zhang Y, Bevilacqua PC, Assmann SM. 30.  2014. In vivo genome-wide profiling of RNA secondary structure reveals novel regulatory features. Nature 505:696–700Describes structure-seq, an in vivo chemical-based structure probing method performed on Arabidopsis seedlings. [Google Scholar]
  31. Donahue CP, Muratore C, Wu JY, Kosik KS, Wolfe MS. 31.  2006. Stabilization of the tau exon 10 stem loop alters pre-mRNA splicing. J. Biol. Chem. 281:23302–6 [Google Scholar]
  32. Dong H, Ray D, Ren S, Zhang B, Puig-Basagoiti F. 32.  et al. 2007. Distinct RNA elements confer specificity to flavivirus RNA cap methylation events. J. Virol. 81:4412–21 [Google Scholar]
  33. Draper DE. 33.  2004. A guide to ions and RNA structure. RNA 10:335–43 [Google Scholar]
  34. Draper DE. 34.  2008. RNA folding: thermodynamic and molecular descriptions of the roles of ions. Biophys. J. 95:5489–95 [Google Scholar]
  35. Ehresmann C, Baudin F, Mougel M, Romby P, Ebel J-P, Ehresmann B. 35.  1987. Probing the structure of RNAs in solution. Nucleic Acid Res. 15:9109–28 [Google Scholar]
  36. Eigen M. 36.  1971. Selforganization of matter and the evolution of biological macromolecules. Naturwissenschaften 58:465–523 [Google Scholar]
  37. Eperon LP, Graham IR, Griffiths AD, Eperon IC. 37.  1988. Effects of RNA secondary structure on alternative splicing of pre-mRNA: Is folding limited to a region behind the transcribing RNA polymerase?. Cell 54:393–401 [Google Scholar]
  38. Estes PA, Cooke NE, Liebhaber SA. 38.  1992. A native RNA secondary structure controls alternative splice-site selection and generates two human growth hormone isoforms. J. Biol. Chem. 267:14902–8 [Google Scholar]
  39. Favorova OO, Fasiolo F, Keith G, Vassilenko SK, Ebel JP. 39.  1981. Partial digestion of tRNA–aminoacyl-tRNA synthetase complexes with cobra venom ribonuclease. Biochemistry 20:1006–11 [Google Scholar]
  40. Fica SM, Tuttle N, Novak T, Li N-S, Lu J. 40.  et al. 2013. RNA catalyses nuclear pre-mRNA splicing. Nature 503:229–34 [Google Scholar]
  41. Flores R, Gago-Zachert S, Serra P, Sanjuán R, Elena SF. 41.  2014. Viroids: survivors from the RNA world?. Annu. Rev. Microbiol. 68:395–414 [Google Scholar]
  42. Foley SW, Vandivier LE, Kuksa PP, Gregory BD. 42.  2015. Transcriptome-wide measurement of plant RNA secondary structure. Curr. Opin. Plant Biol. 27:36–43 [Google Scholar]
  43. Forster AC, Symons RH. 43.  1987. Self-cleavage of plus and minus RNAs of a virusoid and a structural model for the active sites. Cell 49:211–20 [Google Scholar]
  44. Ganot P, Bortolin M-L, Kiss T. 44.  1997. Site-specific pseudouridine formation in preribosomal RNA is guided by small nucleolar RNAs. Cell 89:799–809 [Google Scholar]
  45. Giegé R, Jühling F, Pütz J, Stadler P, Sauter C, Florentz C. 45.  2012. Structure of transfer RNAs: similarity and variability. Wiley Interdiscip. Rev. RNA 3:37–61 [Google Scholar]
  46. Gilbert W. 46.  1986. Origin of life: the RNA world. Nature 319:618 [Google Scholar]
  47. Goodarzi H, Najafabadi HS, Oikonomou P, Greco TM, Fish L. 47.  et al. 2012. Systematic discovery of structural elements governing stability of mammalian messenger RNAs. Nature 485:264–68 [Google Scholar]
  48. Gosai SJ, Foley SW, Wang D, Silverman IM, Selamoglu N. 48.  et al. 2015. Global analysis of the RNA-protein interaction and RNA secondary structure landscapes of the Arabidopsis nucleus. Mol. Cell 57:376–88Describes experiments in which PIP-seq was performed on nuclei extracted from Arabidopsis seedlings, probing both RNA-protein interactions and RNA secondary structure simultaneously. [Google Scholar]
  49. Griffiths-Jones S, Bateman A, Marshall M, Khanna A, Eddy SR. 49.  2003. Rfam: an RNA family database. Nucleic Acids Res. 31:439–41 [Google Scholar]
  50. Gruber AR, Lorenz R, Bernhart SH, Neuböck R, Hofacker IL. 50.  2008. The Vienna RNA websuite. Nucleic Acids Res. 36:W70–74 [Google Scholar]
  51. Grüter P, Tabernero C, von Kobbe C, Schmitt C, Saavedra C. 51.  et al. 1998. TAP, the human homolog of Mex67p, mediates CTE-dependent RNA export from the nucleus. Mol. Cell 1:649–59 [Google Scholar]
  52. Guerrier-Takada C, Gardiner K, Marsh T, Pace N, Altman S. 52.  1983. The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme. Cell 35:849–57 [Google Scholar]
  53. Guttman M, Amit I, Garber M, French C, Lin MF. 53.  et al. 2009. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 458:223–27 [Google Scholar]
  54. Harris KA, Crothers DM, Ullu E. 54.  1995. In vivo structural analysis of spliced leader RNAs in Trypanosoma brucei and Leptomonas collosoma: a flexible structure that is independent of cap4 methylations. RNA 1:351–62 [Google Scholar]
  55. Haugen P, Simon DM, Bhattacharya D. 55.  2005. The natural history of group I introns. Trends Genet. 21:111–19 [Google Scholar]
  56. Hentze MW, Caughman SW, Rouault TA, Barriocanal JG, Dancis A. 56.  et al. 1987. Identification of the iron-responsive element for the translational regulation of human ferritin mRNA. Science 238:1570–73 [Google Scholar]
  57. Heo JB, Sung S. 57.  2011. Vernalization-mediated epigenetic silencing by a long intronic noncoding RNA. Science 331:76–79 [Google Scholar]
  58. Hofacker IL. 58.  2003. Vienna RNA secondary structure server. Nucleic Acids Res. 31:3429–31 [Google Scholar]
  59. Holbrook SR, Kim SH. 59.  1997. RNA crystallography. Biopolymers 44:3–21 [Google Scholar]
  60. Hoogstraten CG, Legault P, Pardi A. 60.  1998. NMR solution structure of the lead-dependent ribozyme: evidence for dynamics in RNA catalysis. J. Mol. Biol. 284:337–50 [Google Scholar]
  61. Inoue T, Cech TR. 61.  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. PNAS 82:648–52 [Google Scholar]
  62. Ivica NA, Obermayer B, Campbell GW, Rajamani S, Gerland U, Chen IA. 62.  2013. The paradox of dual roles in the RNA world: resolving the conflict between stable folding and templating ability. J. Mol. Evol. 77:55–63Uses both experimental and computational approaches to demonstrate the role of wobble base pairing in promoting a division of labor between RNA strands. [Google Scholar]
  63. Jiang W, Hou Y, Inouye M. 63.  1997. CspA, the major cold-shock protein of Escherichia coli, is an RNA chaperone. J. Biol. Chem. 272:196–202 [Google Scholar]
  64. Jin Y, Yang Y, Zhang P. 64.  2011. New insights into RNA secondary structure in the alternative splicing of pre-mRNAs. RNA Biol. 8:450–57 [Google Scholar]
  65. Johansson J, Mandin P, Renzoni A, Chiaruttini C, Springer M, Cossart P. 65.  2002. An RNA thermosensor controls expression of virulence genes in Listeria monocytogenes. Cell 110:551–61 [Google Scholar]
  66. Johnsson P, Lipovich L, Grandér D, Morris KV. 66.  2014. Evolutionary conservation of long non-coding RNAs; sequence, structure, function. Biochim. Biophys. Acta 1840:1063–71 [Google Scholar]
  67. Joyce GF. 67.  1989. RNA evolution and the origins of life. Nature 338:217–24Provides a review of plant RNA chaperones that function to refold their target transcripts in response to cold stress. [Google Scholar]
  68. Kang H, Park SJ, Kwak KJ. 68.  2013. Plant RNA chaperones in stress response. Trends Plant Sci. 18:100–106 [Google Scholar]
  69. Kertesz M, Iovino N, Unnerstall U, Gaul U, Segal E. 69.  2007. The role of site accessibility in microRNA target recognition. Nat. Genet. 39:1278–84 [Google Scholar]
  70. Kertesz M, Wan Y, Mazor E, Rinn JL, Nutter RC. 70.  et al. 2010. Genome-wide measurement of RNA secondary structure in yeast. Nature 467:103–7Describes PARS, one of the first transcriptome-wide structure probing techniques developed in yeast. [Google Scholar]
  71. Kikovska E, Svärd SG, Kirsebom LA. 71.  2007. Eukaryotic RNase P RNA mediates cleavage in the absence of protein. PNAS 104:2062–67 [Google Scholar]
  72. Kilburn D, Roh JH, Guo L, Briber RM, Woodson SA. 72.  2010. Molecular crowding stabilizes folded RNA structure by the excluded volume effect. J. Am. Chem. Soc. 132:8690–96 [Google Scholar]
  73. Kim JS, Park SJ, Kwak KJ, Kim YO, Kim JY. 73.  et al. 2007. Cold shock domain proteins and glycine-rich RNA-binding proteins from Arabidopsis thaliana can promote the cold adaptation process in Escherichia coli. Nucleic Acids Res. 35:506–16 [Google Scholar]
  74. Kim JY, Kim WY, Kwak KJ, Oh SH, Han YS, Kang H. 74.  2010. Glycine-rich RNA-binding proteins are functionally conserved in Arabidopsis thaliana and Oryza sativa during cold adaptation process. J. Exp. Bot. 61:2317–25 [Google Scholar]
  75. Kim MH, Sasaki K, Imai R. 75.  2009. Cold shock domain protein 3 regulates freezing tolerance in Arabidopsis thaliana. J. Biol. Chem. 284:23454–60 [Google Scholar]
  76. Kim SH, Rich A. 76.  1968. Single crystals of transfer RNA: an x-ray diffraction study. Science 162:1381–84 [Google Scholar]
  77. Kim SH, Suddath FL, Quigley GJ, McPherson A, Sussman JL. 77.  et al. 1974. Three-dimensional tertiary structure of yeast phenylalanine transfer RNA. Science 185:435–40 [Google Scholar]
  78. Kiss T. 78.  2002. Small nucleolar RNAs: an abundant group of noncoding RNAs with diverse cellular functions. Cell 109:145–48 [Google Scholar]
  79. Kiss-László Z, Henry Y, Bachellerie J-P, Caizergues-Ferrer M, Kiss T. 79.  1996. Site-specific ribose methylation of preribosomal RNA: a novel function for small nucleolar RNAs. Cell 85:1077–88 [Google Scholar]
  80. Klasens BI, Das AT, Berkhout B. 80.  1998. Inhibition of polyadenylation by stable RNA secondary structure. Nucleic Acids Res. 26:1870–76 [Google Scholar]
  81. Knapp G. 81.  1989. Enzymatic approaches to probing of RNA secondary and tertiary structure. Methods Enzymol. 180:192–212 [Google Scholar]
  82. Kortmann J, Narberhaus F. 82.  2012. Bacterial RNA thermometers: molecular zippers and switches. Nat. Rev. Microbiol. 10:255–65 [Google Scholar]
  83. Kozak M. 83.  1986. Influences of mRNA secondary structure on initiation by eukaryotic ribosomes. PNAS 83:2850–54 [Google Scholar]
  84. Kozak M. 84.  1988. Leader length and secondary structure modulate mRNA function under conditions of stress. Mol. Cell. Biol. 8:2737–44 [Google Scholar]
  85. Kruger K, Grabowski PJ, Zaug AJ, Sands J, Gottschling DE, Cech TR. 85.  1982. Self-splicing RNA: autoexcision and autocyclization of the ribosomal RNA intervening sequence of Tetrahymena. Cell 31:147–57 [Google Scholar]
  86. Kun Á, Santos M, Szathmáry E. 86.  2005. Real ribozymes suggest a relaxed error threshold. Nat. Genet. 37:1008–11 [Google Scholar]
  87. Kun Á, Szilágyi A, Könnyű B, Boza G, Zachar I, Szathmáry E. 87.  2015. The dynamics of the RNA world: insights and challenges. Ann. N.Y. Acad. Sci. 1341:75–95 [Google Scholar]
  88. Kuninaka A, Kibi M, Yoshino H, Sakaguchi K. 88.  1961. Studies on 5′-phosphodiesterases in microorganisms. Agric. Biol. Chem. 25:693–701 [Google Scholar]
  89. Kurihara Y, Watanabe Y. 89.  2004. Arabidopsis micro-RNA biogenesis through Dicer-like 1 protein functions. PNAS 101:12753–58 [Google Scholar]
  90. Kwak KJ, Kim YO, Kang H. 90.  2005. Characterization of transgenic Arabidopsis plants overexpressing GR-RBP4 under high salinity, dehydration, or cold stress. J. Exp. Bot. 56:3007–16 [Google Scholar]
  91. Lambert D, Draper DE. 91.  2007. Effects of osmolytes on RNA secondary and tertiary structure stabilities and RNA-Mg2+ interactions. J. Mol. Biol. 370:993–1005 [Google Scholar]
  92. Law JA, Jacobsen SE. 92.  2010. Establishing, maintaining and modifying DNA methylation patterns in plants and animals. Nat. Rev. Genet. 11:204–20 [Google Scholar]
  93. Lawley PD, Brookes P. 93.  1963. Further studies on the alkylation of nucleic acids and their constituent nucleotides. Biochem. J. 89:127–38 [Google Scholar]
  94. Lawrence MS, Bartel DP. 94.  2003. Processivity of ribozyme-catalyzed RNA polymerization. Biochemistry 42:8748–55 [Google Scholar]
  95. Lazcano A, Miller SL. 95.  1996. The origin and early evolution of life: prebiotic chemistry, the pre-RNA world, and time. Cell 85:793–98 [Google Scholar]
  96. Lempereur L, Nicoloso M, Riehl N, Ehresmann C, Ehresmann B, Bachellerie JP. 96.  1985. Conformation of yeast 18S rRNA. Direct chemical probing of the 5′ domain in ribosomal subunits and in deproteinized RNA by reverse transcriptase mapping of dimethyl sulfate-accessible sites. Nucleic Acids Res. 13:8339–57 [Google Scholar]
  97. Leontis NB, Westhof E. 97.  2001. Geometric nomenclature and classification of RNA base pairs. RNA 7:499–512 [Google Scholar]
  98. Lestrade L, Weber MJ. 98.  2006. snoRNA-LBME-db, a comprehensive database of human H/ACA and C/D box snoRNAs. Nucleic Acids Res. 34:Suppl. 1D158–62 [Google Scholar]
  99. Li F, Zheng Q, Ryvkin P, Dragomir I, Desai Y. 99.  et al. 2012. Global analysis of RNA secondary structure in two metazoans. Cell Rep. 1:69–82 [Google Scholar]
  100. Li F, Zheng Q, Vandivier LE, Willmann MR, Chen Y, Gregory BD. 100.  2012. Regulatory impact of RNA secondary structure across the Arabidopsis transcriptome. Plant Cell 24:4346–59Describes experiments in which dsRNA/ssRNA-seq was performed in flower buds from Arabidopsis, revealing many transcriptome-wide structural features. [Google Scholar]
  101. Lim PO, Sears BB. 101.  1989. 16S rRNA sequence indicates that plant-pathogenic mycoplasmalike organisms are evolutionarily distinct from animal mycoplasmas. J. Bacteriol. 171:5901–6 [Google Scholar]
  102. Liu HX, Goodall GJ, Kole R, Filipowicz W. 102.  1995. Effects of secondary structure on pre-mRNA splicing: Hairpins sequestering the 5′ but not the 3′ splice site inhibit intron processing in Nicotiana plumbaginifolia. EMBO J. 14:377–88 [Google Scholar]
  103. Liu N, Dai Q, Zheng G, He C, Parisien M, Pan T. 103.  2015. N6-methyladenosine-dependent RNA structural switches regulate RNA-protein interactions. Nature 518:560–64 [Google Scholar]
  104. Liu X, Hao L, Li D, Zhu L, Hu S. 104.  2015. Long non-coding RNAs and their biological roles in plants. Genom. Proteom. Bioinform. 13:137–47 [Google Scholar]
  105. Lockard RE, Kumar A. 105.  1981. Mapping tRNA structure in solution using double-strand-specific ribonuclease V1 from cobra venom. Nucleic Acids Res. 9:5125–40 [Google Scholar]
  106. Lorsch JR. 106.  2002. RNA chaperones exist and DEAD box proteins get a life. Cell 109:797–800 [Google Scholar]
  107. Loverix S, Steyaert J. 107.  2001. Deciphering the mechanism of RNase T1. Methods Enzymol. 341:305–23 [Google Scholar]
  108. Lu D, Searles MA, Klug A. 108.  2003. Crystal structure of a zinc-finger-RNA complex reveals two modes of molecular recognition. Nature 426:96–100 [Google Scholar]
  109. Ludwig W, Strunk O, Klugbauer S, Klugbauer N, Weizenegger M. 109.  et al. 1998. Bacterial phylogeny based on comparative sequence analysis (review). Electrophoresis 19:554–68 [Google Scholar]
  110. Lunde BM, Moore C, Varani G. 110.  2007. RNA-binding proteins: modular design for efficient function. Nat. Rev. Mol. Cell Biol. 8:479–90 [Google Scholar]
  111. Madhani HD. 111.  2013. snRNA catalysts in the spliceosome's ancient core. Cell 155:1213–15 [Google Scholar]
  112. Mathews DH. 112.  2014. RNA secondary structure analysis using RNAstructure. Curr. Protoc. Bioinform. 46:12.6.1–25 [Google Scholar]
  113. Mathews DH, Disney MD, Childs JL, Schroeder SJ, Zuker M, Turner DH. 113.  2004. Incorporating chemical modification constraints into a dynamic programming algorithm for prediction of RNA secondary structure. PNAS 101:7287–92 [Google Scholar]
  114. McClung CR, Davis SJ. 114.  2010. Ambient thermometers in plants: from physiological outputs towards mechanisms of thermal sensing. Curr. Biol. 20:R1086–92 [Google Scholar]
  115. Mercer TR, Mattick JS. 115.  2013. Structure and function of long noncoding RNAs in epigenetic regulation. Nat. Struct. Mol. Biol. 20:300–307 [Google Scholar]
  116. Merino EJ, Wilkinson KA, Coughlan JL, Weeks KM. 116.  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]
  117. Miranda-Ríos J. 117.  2007. The THI-box riboswitch, or how RNA binds thiamin pyrophosphate. Structure 15:259–65 [Google Scholar]
  118. Moazed D, Noller HF. 118.  1987. Chloramphenicol, erythromycin, carbomycin and vernamycin B protect overlapping sites in the peptidyl transferase region of 23S ribosomal RNA. Biochimie 69:879–84 [Google Scholar]
  119. Moazed D, Noller HF. 119.  1987. Interaction of antibiotics with functional sites in 16S ribosomal RNA. Nature 327:389–94 [Google Scholar]
  120. Mohr S, Stryker JM, Lambowitz AM. 120.  2002. A DEAD-box protein functions as an ATP-dependent RNA chaperone in group I intron splicing. Cell 109:769–79 [Google Scholar]
  121. Møller T, Franch T, Højrup P, Keene DR, Bächinger HP. 121.  et al. 2002. Hfq: a bacterial Sm-like protein that mediates RNA-RNA interaction. Mol. Cell 9:23–30 [Google Scholar]
  122. Nakaminami K, Karlson DT, Imai R. 122.  2006. Functional conservation of cold shockdomains in bacteria and higher plants. PNAS 103:10122–27 [Google Scholar]
  123. Narberhaus F. 123.  2010. Translational control of bacterial heat shock and virulence genes by temperature-sensing mRNAs. RNA Biol. 7:84–89 [Google Scholar]
  124. Ni J, Tien AL, Fournier MJ. 124.  1997. Small nucleolar RNAs direct site-specific synthesis of pseudouridine in ribosomal RNA. Cell 89:565–73 [Google Scholar]
  125. Nissen P, Hansen J, Ban N, Moore PB, Steitz TA. 125.  2000. The structural basis of ribosome activity in peptide bond synthesis. Science 289:920–30 [Google Scholar]
  126. Novikova IV, Hennelly SP, Sanbonmatsu KY. 126.  2012. Sizing up long non-coding RNAs: Do lncRNAs have secondary and tertiary structure?. BioArchitecture 2:189–99 [Google Scholar]
  127. Oberstrass FC, Lee A, Stefl R, Janis M, Chanfreau G, Allain FH-T. 127.  2006. Shape-specific recognition in the structure of the Vts1p SAM domain with RNA. Nat. Struct. Mol. Biol. 13:160–67 [Google Scholar]
  128. Oikawa D, Tokuda M, Hosoda A, Iwawaki T. 128.  2010. Identification of a consensus element recognized and cleaved by IRE1α. Nucleic Acids Res. 38:6265–73 [Google Scholar]
  129. Oliverio M, Cervelli M, Mariottini P. 129.  2002. ITS2 rRNA evolution and its congruence with the phylogeny of muricid neogastropods (Caenogastropoda, Muricoidea). Mol. Phylogenet. Evol. 25:63–69 [Google Scholar]
  130. Oubridge C, Ito N, Evans PR, Teo C-H, Nagai K. 130.  1994. Crystal structure at 1.92 Å resolution of the RNA-binding domain of the U1a spliceosomal protein complexed with an RNA hairpin. Nature 372:432–38 [Google Scholar]
  131. Park W, Li J, Song R, Messing J, Chen X. 131.  2002. CARPEL FACTORY, a dicer homolog, and HEN1, a novel protein, act in microRNA metabolism in Arabidopsis thaliana. Curr. Biol. 12:1484–95 [Google Scholar]
  132. Peattie DA. 132.  1979. Direct chemical method for sequencing RNA. PNAS 76:1760–64 [Google Scholar]
  133. Peattie DA, Gilbert W. 133.  1980. Chemical probes for higher-order structure in RNA. PNAS 77:4679–82 [Google Scholar]
  134. Pelletier J, Sonenberg N. 134.  1985. Insertion mutagenesis to increase secondary structure within the 5′ noncoding region of a eukaryotic mRNA reduces translational efficiency. Cell 40:515–26 [Google Scholar]
  135. Pelletier J, Sonenberg N. 135.  1988. Internal initiation of translation of eukaryotic mRNA directed by a sequence derived from poliovirus RNA. Nature 334:320–25 [Google Scholar]
  136. Phadtare S, Inouye M, Severinov K. 136.  2002. The nucleic acid melting activity of Escherichia coli CspE is critical for transcription antitermination and cold acclimation of cells. J. Biol. Chem. 277:7239–45 [Google Scholar]
  137. Ponjavic J, Ponting CP, Lunter G. 137.  2007. Functionality or transcriptional noise? Evidence for selection within long noncoding RNAs. Genome Res. 17:556–65 [Google Scholar]
  138. Ponting CP, Oliver PL, Reik W. 138.  2009. Evolution and functions of long noncoding RNAs. Cell 136:629–41 [Google Scholar]
  139. Rajkowitsch L, Chen D, Stampfl S, Semrad K, Waldsich C. 139.  et al. 2007. RNA chaperones, RNA annealers and RNA helicases. RNA Biol. 4:118–30 [Google Scholar]
  140. Raker VA, Mironov AA, Gelfand MS, Pervouchine DD. 140.  2009. Modulation of alternative splicing by long-range RNA structures in Drosophila. Nucleic Acids Res. 37:4533–44 [Google Scholar]
  141. Ramakrishnan V. 141.  2014. The ribosome emerges from a black box. Cell 159:979–84 [Google Scholar]
  142. Ramani V, Qui R, Shendure J. 142.  2015. High-throughput determination of RNA structure by proximity ligation. Nat. Biotechnol. 33:980–84 [Google Scholar]
  143. Reinhart BJ, Weinstein EG, Rhoades MW, Bartel B, Bartel DP. 143.  2002. MicroRNAs in plants. Genes Dev. 16:1616–26 [Google Scholar]
  144. Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X. 144.  et al. 2007. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 129:1311–23 [Google Scholar]
  145. Robertus JD, Ladner JE, Finch JT, Rhodes D, Brown RS. 145.  et al. 1974. Structure of yeast phenylalanine tRNA at 3 Å resolution. Nature 250:546–51 [Google Scholar]
  146. Roth A, Breaker RR. 146.  2009. The structural and functional diversity of metabolite-binding riboswitches. Annu. Rev. Biochem. 78:305–34 [Google Scholar]
  147. Rouskin S, Zubradt M, Washietl S, Kellis M, Weissman JS. 147.  2014. Genome-wide probing of RNA structure reveals active unfolding of mRNA structures in vivo. Nature 505:701–5 [Google Scholar]
  148. Ryter JM. 148.  1998. Molecular basis of double-stranded RNA-protein interactions: structure of a dsRNA-binding domain complexed with dsRNA. EMBO J. 17:7505–13 [Google Scholar]
  149. Sasaki K, Imai R. 149.  2012. Pleiotropic roles of cold shock domain proteins in plants. Front. Plant Sci. 2:116 [Google Scholar]
  150. Schlötterer C, Hauser MT, von Haeseler A, Tautz D. 150.  1994. Comparative evolutionary analysis of rDNA ITS regions in Drosophila. Mol. Biol. Evol. 11:513–22 [Google Scholar]
  151. Schroeder R, Barta A, Semrad K. 151.  2004. Strategies for RNA folding and assembly. Nat. Rev. Mol. Cell Biol. 5:908–19 [Google Scholar]
  152. Schwarz Z, Kössel H. 152.  1980. The primary structure of 16s rDNA from Zea mays chloroplast is homologous to E. coli 16S rRNA. Nature 283:739–42 [Google Scholar]
  153. Serganov A, Patel DJ. 153.  2007. Ribozymes, riboswitches and beyond: regulation of gene expression without proteins. Nat. Rev. Genet. 8:776–90 [Google Scholar]
  154. Shabalina SA, Ogurtsov AY, Spiridonov NA. 154.  2006. A periodic pattern of mRNA secondary structure created by the genetic code. Nucleic Acids Res. 34:2428–37 [Google Scholar]
  155. Shen LX, Basilion JP, Stanton VP. 155.  1999. Single-nucleotide polymorphisms can cause different structural folds of mRNA. PNAS 96:7871–76 [Google Scholar]
  156. Silverman IM, Li F, Alexander A, Goff L, Trapnell C. 156.  et al. 2014. RNase-mediated protein footprint sequencing reveals protein-binding sites throughout the human transcriptome. Genome Biol. 15:R3 [Google Scholar]
  157. Sirand-Pugnet P, Durosay P, Clouet d'Orval BC, Brody E, Marie J. 157.  1995. β-Tropomyosin pre-mRNA folding around a muscle-specific exon interferes with several steps of spliceosome assembly. J. Mol. Biol. 251:591–602 [Google Scholar]
  158. Solnick D. 158.  1985. Alternative splicing caused by RNA secondary structure. Cell 43:667–76 [Google Scholar]
  159. Somarowthu S, Legiewicz M, Chillón I, Marcia M, Liu F, Pyle AM. 159.  2015. HOTAIR forms an intricate and modular secondary structure. Mol. Cell 58:353–61 [Google Scholar]
  160. Spitale RC, Flynn RA, Zhang QC, Crisalli P, Lee B. 160.  et al. 2015. Structural imprints in vivo decode RNA regulatory mechanisms. Nature 519:486–90Describes icSHAPE, the first high-throughput chemical-based structure probing technique that probes ssRNA without nucleotide bias. [Google Scholar]
  161. Springer MS, Douzery E. 161.  1996. Secondary structure and patterns of evolution among mammalian mitochondrial 12S rRNA molecules. J. Mol. Evol. 43:357–73 [Google Scholar]
  162. Steitz TA, Moore PB. 162.  2003. RNA, the first macromolecular catalyst: The ribosome is a ribozyme. Trends Biochem. Sci. 28:411–18 [Google Scholar]
  163. Subramanian M, Rage F, Tabet R, Flatter E, Mandel J-L, Moine H. 163.  2011. G-quadruplex RNA structure as a signal for neurite mRNA targeting. EMBO Rep. 12:697–704 [Google Scholar]
  164. Suo Z, Johnson KA. 164.  1997. Effect of RNA secondary structure on the kinetics of DNA synthesis catalyzed by HIV-1 reverse transcriptase. Biochemistry 36:12459–67 [Google Scholar]
  165. Svitkin YV, Pause A, Haghighat A, Pyronnet S, Witherell G. 165.  et al. 2001. The requirement for eukaryotic initiation factor 4A (eIF4A) in translation is in direct proportion to the degree of mRNA 5′ secondary structure. RNA 7:382–94 [Google Scholar]
  166. Swiezewski S, Liu F, Magusin A, Dean C. 166.  2009. Cold-induced silencing by long antisense transcripts of an Arabidopsis polycomb target. Nature 462:799–802 [Google Scholar]
  167. Talkish J, May G, Lin Y, Woolford JL Jr, McManus CJ. 167.  2014. Mod-seq: high-throughput sequencing for chemical probing of RNA structure. RNA 20:1–8 [Google Scholar]
  168. Tenenbaum SA, Christiansen J, Nielsen H. 168.  2011. The post-transcriptional operon. Methods Mol. Biol. 703:237–45 [Google Scholar]
  169. Thirumalai D, Hyeon C. 169.  2009. Theory of RNA folding: from hairpins to ribozymes. Non-Protein Coding RNAs DNG Walter, DSA Woodson, DRT Batey 27–47 Berlin: Springer [Google Scholar]
  170. Tompa P, Csermely P. 170.  2004. The role of structural disorder in the function of RNA and protein chaperones. FASEB J. 18:1169–75 [Google Scholar]
  171. Uchida T, Arima T, Egami F. 171.  1970. Specificity of RNase U2. J. Biochem. 67:91–102 [Google Scholar]
  172. Ulitsky I, Shkumatava A, Jan CH, Sive H, Bartel DP. 172.  2011. Conserved function of lincRNAs in vertebrate embryonic development despite rapid sequence evolution. Cell 147:1537–50 [Google Scholar]
  173. Underwood JG, Uzilov AV, Katzman S, Onodera CS, Mainzer JE. 173.  et al. 2010. FragSeq: transcriptome-wide RNA structure probing using high-throughput sequencing. Nat. Methods 7:995–1001 [Google Scholar]
  174. Vandivier L, Li F, Zheng Q, Willmann M, Chen Y, Gregory B. 174.  2013. Arabidopsis mRNA secondary structure correlates with protein function and domains. Plant Signal. Behav. 8:e24301 [Google Scholar]
  175. Vitreschak AG, Rodionov DA, Mironov AA, Gelfand MS. 175.  2004. Riboswitches: the oldest mechanism for the regulation of gene expression?. Trends Genet. 20:44–50 [Google Scholar]
  176. Vogel J. 176.  2002. Lariat formation and a hydrolytic pathway in plant chloroplast group II intron splicing. EMBO J. 21:3794–803 [Google Scholar]
  177. Volkin E, Cohn WE. 177.  1953. On the structure of ribonucleic acids. II. The products of ribonuclease action. J. Biol. Chem. 205:767–82 [Google Scholar]
  178. Wan Y, Qu K, Zhang QC, Flynn RA, Manor O. 178.  et al. 2014. Landscape and variation of RNA secondary structure across the human transcriptome. Nature 505:706–9 [Google Scholar]
  179. Wang KC, Chang HY. 179.  2011. Molecular mechanisms of long noncoding RNAs. Mol. Cell 43:904–14 [Google Scholar]
  180. Wang L, Wessler SR. 180.  2001. Role of mRNA secondary structure in translational repression of the maize transcriptional activator Lc. Plant Physiol. 125:1380–87 [Google Scholar]
  181. Wanrooij PH, Uhler JP, Simonsson T, Falkenberg M, Gustafsson CM. 181.  2010. G-quadruplex structures in RNA stimulate mitochondrial transcription termination and primer formation. PNAS 107:16072–77 [Google Scholar]
  182. Warf MB, Berglund JA. 182.  2010. Role of RNA structure in regulating pre-mRNA splicing. Trends Biochem. Sci. 35:169–78 [Google Scholar]
  183. Wells SE, Hughes JM, Igel AH, Ares M. 183.  2000. Use of dimethyl sulfate to probe RNA structure in vivo. Methods Enzymol. 318:479–93 [Google Scholar]
  184. Wen J-D, Lancaster L, Hodges C, Zeri A-C, Yoshimura SH. 184.  et al. 2008. Following translation by single ribosomes one codon at a time. Nature 452:598–603 [Google Scholar]
  185. Wilkinson KA, Merino EJ, Weeks KM. 185.  2006. Selective 2′-hydroxyl acylation analyzed by primer extension (SHAPE): quantitative RNA structure analysis at single nucleotide resolution. Nat. Protoc. 1:1610–16 [Google Scholar]
  186. Williams AS, Marzluff WF. 186.  1995. The sequence of the stem and flanking sequences at the 3′ end of histone mRNA are critical determinants for the binding of the stem-loop binding protein. Nucleic Acids Res. 23:654–62 [Google Scholar]
  187. Williamson JR. 187.  2000. Induced fit in RNA-protein recognition. Nat. Struct. Mol. Biol. 7:834–37 [Google Scholar]
  188. Winkler WC, Nahvi A, Roth A, Collins JA, Breaker RR. 188.  2004. Control of gene expression by a natural metabolite-responsive ribozyme. Nature 428:281–86 [Google Scholar]
  189. Yang C-H, Crowley DE. 189.  2000. Rhizosphere microbial community structure in relation to root location and plant iron nutritional status. Appl. Environ. Microbiol. 66:345–51 [Google Scholar]
  190. Yusupova G, Yusupov M. 190.  2014. High-resolution structure of the eukaryotic 80S ribosome. Annu. Rev. Biochem. 83:467–86 [Google Scholar]
  191. Zappulla DC, Cech TR. 191.  2004. Yeast telomerase RNA: a flexible scaffold for protein subunits. PNAS 101:10024–29 [Google Scholar]
  192. Zaug AJ, Cech TR. 192.  1995. Analysis of the structure of Tetrahymena nuclear RNAs in vivo: telomerase RNA, the self-splicing rTNA intron, and U2 snRNA. RNA 1:363–74 [Google Scholar]
  193. Zhao B, Zhang Q. 193.  2015. Characterizing excited conformational states of RNA by NMR spectroscopy. Curr. Opin. Struct. Biol. 30:134–46Describes the utility of NMR and its ability to study RNA folding dynamics. [Google Scholar]
  194. Zheng Q, Ryvkin P, Li F, Dragomir I, Valladares O. 194.  et al. 2010. Genome-wide double-stranded RNA sequencing reveals the functional significance of base-paired RNAs in Arabidopsis. PLOS Genet. 6:e1001141Describes the use of dsRNA-seq, the first transcriptome-wide structure probing technique performed in plants, to identify dsRNA in Arabidopsis flower buds. [Google Scholar]
  195. Zuker M, Stiegler P. 195.  1981. Optimal computer folding of large RNA sequences using thermodynamics and auxiliary information. Nucleic Acids Res. 9:133–48 [Google Scholar]

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error