RNA dynamics play a fundamental role in many cellular functions. However, there is no general framework to describe these complex processes, which typically consist of many structural maneuvers that occur over timescales ranging from picoseconds to seconds. Here, we classify RNA dynamics into distinct modes representing transitions between basins on a hierarchical free-energy landscape. These transitions include large-scale secondary-structural transitions at >0.1-s timescales, base-pair/tertiary dynamics at microsecond-to-millisecond timescales, stacking dynamics at timescales ranging from nanoseconds to microseconds, and other “jittering” motions at timescales ranging from picoseconds to nanoseconds. We review various modes within these three different tiers, the different mechanisms by which they are used to regulate function, and how they can be coupled together to achieve greater functional complexity.


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Literature Cited

  1. Kruger K, Grabowski PJ, Zaug AJ, Sands J, Gottschling DE, Cech TR. 1.  1982. Self-splicing RNA: autoexcision and autocyclization of the ribosomal RNA intervening sequence of Tetrahymena. Cell 31:147–57 [Google Scholar]
  2. Guerrier-Takada C, Gardiner K, Marsh T, Pace N, Altman S. 2.  1983. The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme. Cell 35:849–57 [Google Scholar]
  3. Serganov A, Patel DJ. 3.  2012. Metabolite recognition principles and molecular mechanisms underlying riboswitch function. Annu. Rev. Biophys. 41:343–70 [Google Scholar]
  4. Reiter NJ, Chan CW, Mondragon A. 4.  2011. Emerging structural themes in large RNA molecules. Curr. Opin. Struct. Biol. 21:319–26 [Google Scholar]
  5. Voorhees RM, Ramakrishnan V. 5.  2013. Structural basis of the translational elongation cycle. Annu. Rev. Biochem. 82:203–36 [Google Scholar]
  6. Djebali S, Davis CA, Merkel A, Dobin A, Lassmann T. 6.  et al. 2012. Landscape of transcription in human cells. Nature 489:101–8 [Google Scholar]
  7. Bernstein BE, Birney E, Dunham I, Green ED, Gunter C, Snyder M. 7.  2012. An integrated encyclopedia of DNA elements in the human genome. Nature 489:57–74 [Google Scholar]
  8. Zaher HS, Green R. 8.  2009. Fidelity at the molecular level: lessons from protein synthesis. Cell 136:746–62 [Google Scholar]
  9. Cruz JA, Westhof E. 9.  2009. The dynamic landscapes of RNA architecture. Cell 136:604–9 [Google Scholar]
  10. Dethoff EA, Chugh J, Mustoe AM, Al-Hashimi HM. 10.  2012. Functional complexity and regulation through RNA dynamics. Nature 482:322–30 [Google Scholar]
  11. Frauenfelder H, Sligar SG, Wolynes PG. 11.  1991. The energy landscapes and motions of proteins. Science 254:1598–603 [Google Scholar]
  12. Tinoco I Jr, Bustamante C. 12.  1999. How RNA folds. J. Mol. Biol. 293:271–81 [Google Scholar]
  13. Brion P, Westhof E. 13.  1997. Hierarchy and dynamics of RNA folding. Annu. Rev. Biophys. Biomol. Struct. 26:113–37 [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. McCaskill JS.15.  1990. The equilibrium partition function and base pair binding probabilities for RNA secondary structure. Biopolymers 29:1105–19 [Google Scholar]
  16. Wuchty S, Fontana W, Hofacker IL, Schuster P. 16.  1999. Complete suboptimal folding of RNA and the stability of secondary structures. Biopolymers 49:145–65 [Google Scholar]
  17. Uhlenbeck OC.17.  1995. Keeping RNA happy. RNA 1:4–6 [Google Scholar]
  18. Treiber DK, Williamson JR. 18.  2001. Beyond kinetic traps in RNA folding. Curr. Opin. Struct. Biol. 11:309–14 [Google Scholar]
  19. Fürtig B, Wenter P, Reymond L, Richter C, Pitsch S, Schwalbe H. 19.  2007. Conformational dynamics of bistable RNAs studied by time-resolved NMR spectroscopy. J. Am. Chem. Soc. 129:16222–29 [Google Scholar]
  20. Xu X, Chen S-J. 20.  2012. Kinetic mechanism of conformational switch between bistable RNA hairpins. J. Am. Chem. Soc. 134:12499–507 [Google Scholar]
  21. Grohman JK, Gorelick RJ, Lickwar CR, Lieb JD, Bower BD. 21.  et al. 2013. A guanosine-centric mechanism for RNA chaperone function. Science 340:190–95 [Google Scholar]
  22. Herschlag D.22.  1995. RNA chaperones and the RNA folding problem. J. Biol. Chem. 270:20871–74 [Google Scholar]
  23. Thirumalai D, Woodson SA. 23.  1996. Kinetics of folding of proteins and RNA. Acc. Chem. Res. 29:433–39 [Google Scholar]
  24. Breaker RR.24.  2012. Riboswitches and the RNA world. Cold Spring Harb. Perspect. Biol. 4:a003566 [Google Scholar]
  25. Winkler W, Nahvi A, Breaker RR. 25.  2002. Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expression. Nature 419:952–56 [Google Scholar]
  26. Caron MP, Bastet L, Lussier A, Simoneau-Roy M, Masse E, Lafontaine DA. 26.  2012. Dual-acting riboswitch control of translation initiation and mRNA decay. Proc. Natl. Acad. Sci. USA 109:E3444–53 [Google Scholar]
  27. Cheah MT, Wachter A, Sudarsan N, Breaker RR. 27.  2007. Control of alternative RNA splicing and gene expression by eukaryotic riboswitches. Nature 447:497–500 [Google Scholar]
  28. Mironov AS, Gusarov I, Rafikov R, Lopez LE, Shatalin K. 28.  et al. 2002. Sensing small molecules by nascent RNA: a mechanism to control transcription in bacteria. Cell 111:747–56 [Google Scholar]
  29. Haller A, Soulière MF, Micura R. 29.  2011. The dynamic nature of RNA as key to understanding riboswitch mechanisms. Acc. Chem. Res. 44:1339–48 [Google Scholar]
  30. Kortmann J, Sczodrok S, Rinnenthal J, Schwalbe H, Narberhaus F. 30.  2011. Translation on demand by a simple RNA-based thermosensor. Nucleic Acids Res. 39:2855–68 [Google Scholar]
  31. Reining A, Nozinovic S, Schlepckow K, Buhr F, Fürtig B, Schwalbe H. 31.  2013. Three-state mechanism couples ligand and temperature sensing in riboswitches. Nature 499:355–59 [Google Scholar]
  32. Giuliodori AM, Di Pietro F, Marzi S, Masquida B, Wagner R. 32.  et al. 2010. The cspA mRNA is a thermosensor that modulates translation of the cold-shock protein CspA. Mol. Cell 37:21–33 [Google Scholar]
  33. Cromie MJ, Shi Y, Latifi T, Groisman EA. 33.  2006. An RNA sensor for intracellular Mg2+. Cell 125:71–84 [Google Scholar]
  34. Nechooshtan G, Elgrably-Weiss M, Sheaffer A, Westhof E, Altuvia S. 34.  2009. A pH-responsive riboregulator. Genes Dev. 23:2650–62 [Google Scholar]
  35. Babitzke P, Yanofsky C. 35.  1993. Reconstitution of Bacillus subtilis trp attenuation in vitro with TRAP, the trp RNA-binding attenuation protein. Proc. Natl. Acad. Sci. USA 90:133–37 [Google Scholar]
  36. Grundy FJ, Winkler WC, Henkin TM. 36.  2002. tRNA-mediated transcription antitermination in vitro: codon–anticodon pairing independent of the ribosome. Proc. Natl. Acad. Sci. USA 99:11121–26 [Google Scholar]
  37. Vogel J, Luisi BF. 37.  2011. Hfq and its constellation of RNA. Nat. Rev. Microbiol. 9:578–89 [Google Scholar]
  38. Semlow DR, Staley JP. 38.  2012. Staying on message: ensuring fidelity in pre-mRNA splicing. Trends Biochem. Sci. 37:263–73 [Google Scholar]
  39. Huthoff H, Berkhout B. 39.  2001. Two alternating structures of the HIV-1 leader RNA. RNA 7:143–57 [Google Scholar]
  40. Lu K, Heng X, Summers MF. 40.  2011. Structural determinants and mechanism of HIV-1 genome packaging. J. Mol. Biol. 410:609–33 [Google Scholar]
  41. Lu K, Heng X, Garyu L, Monti S, Garcia EL. 41.  et al. 2011. NMR detection of structures in the HIV-1 5′-leader RNA that regulate genome packaging. Science 334:242–45 [Google Scholar]
  42. Snoussi K, Leroy JL. 42.  2001. Imino proton exchange and base-pair kinetics in RNA duplexes. Biochemistry 40:8898–904 [Google Scholar]
  43. Chen C, Jiang L, Michalczyk R, Russu IM. 43.  2006. Structural energetics and base-pair opening dynamics in sarcin–ricin domain RNA. Biochemistry 45:13606–13 [Google Scholar]
  44. Rinnenthal J, Klinkert B, Narberhaus F, Schwalbe H. 44.  2010. Direct observation of the temperature-induced melting process of the Salmonella fourU RNA thermometer at base-pair resolution. Nucleic Acids Res. 38:3834–47 [Google Scholar]
  45. Woodson SA.45.  2010. Taming free energy landscapes with RNA chaperones. RNA Biol. 7:677–86 [Google Scholar]
  46. Jankowsky E.46.  2011. RNA helicases at work: binding and rearranging. Trends Biochem. Sci. 36:19–29 [Google Scholar]
  47. Shankar N, Xia T, Kennedy SD, Krugh TR, Mathews DH, Turner DH. 47.  2007. NMR reveals the absence of hydrogen bonding in adjacent UU and AG mismatches in an isolated internal loop from ribosomal RNA. Biochemistry 46:12665–78 [Google Scholar]
  48. Conn GL, Draper DE, Lattman EE, Gittis AG. 48.  1999. Crystal structure of a conserved ribosomal protein–RNA complex. Science 284:1171–74 [Google Scholar]
  49. Wang Y-X, Huang S, Draper DE. 49.  1996. Structure of a U–U pair within a conserved ribosomal RNA hairpin. Nucleic Acids Res. 24:2666–72 [Google Scholar]
  50. Mustoe AM, Bailor MH, Teixeira RM, Brooks CL III, Al-Hashimi HM. 50.  2012. New insights into the fundamental role of topological constraints as a determinant of two-way junction conformation. Nucleic Acids Res. 40:892–904 [Google Scholar]
  51. Schmeing TM, Huang KS, Strobel SA, Steitz TA. 51.  2005. An induced-fit mechanism to promote peptide bond formation and exclude hydrolysis of peptidyl-tRNA. Nature 438:520–24 [Google Scholar]
  52. Qu X, Wen JD, Lancaster L, Noller HF, Bustamante C, Tinoco I Jr. 52.  2011. The ribosome uses two active mechanisms to unwind messenger RNA during translation. Nature 475:118–21 [Google Scholar]
  53. Watts JM, Dang KK, Gorelick RJ, Leonard CW, Bess JW Jr. 53.  et al. 2009. Architecture and secondary structure of an entire HIV-1 RNA genome. Nature 460:711–16 [Google Scholar]
  54. Mouzakis KD, Lang AL, Vander Meulen KA, Easterday PD, Butcher SE. 54.  2013. HIV-1 frameshift efficiency is primarily determined by the stability of base pairs positioned at the mRNA entrance channel of the ribosome. Nucleic Acids Res. 41:1901–13 [Google Scholar]
  55. Dethoff EA, Petzold K, Chugh J, Casiano-Negroni A, Al-Hashimi HM. 55.  2012. Visualizing transient low-populated structures of RNA. Nature 491:724–28 [Google Scholar]
  56. Hoogstraten CG, Wank JR, Pardi A. 56.  2000. Active site dynamics in the lead-dependent ribozyme. Biochemistry 39:9951–58 [Google Scholar]
  57. Venditti V, Clos L 2nd, Niccolai N, Butcher SE. 57.  2009. Minimum-energy path for a U6 RNA conformational change involving protonation, base-pair rearrangement and base flipping. J. Mol. Biol. 391:894–905 [Google Scholar]
  58. Reiter NJ, Blad H, Abildgaard F, Butcher SE. 58.  2004. Dynamics in the U6 RNA intramolecular stem-loop: a base flipping conformational change. Biochemistry 43:13739–47 [Google Scholar]
  59. Nikolova EN, Kim E, Wise AA, O'Brien PJ, Andricioaei I, Al-Hashimi HM. 59.  2011. Transient Hoogsteen base pairs in canonical duplex DNA. Nature 470:498–502 [Google Scholar]
  60. Nikolova EN, Goh GB, Brooks CL III, Al-Hashimi HM. 60.  2013. Characterizing the protonation state of cytosine in transient G·C Hoogsteen base pairs in duplex DNA. J. Am. Chem. Soc. 135:6766–69 [Google Scholar]
  61. Yajima R, Proctor DJ, Kierzek R, Kierzek E, Bevilacqua PC. 61.  2007. A conformationally restricted guanosine analog reveals the catalytic relevance of three structures of an RNA enzyme. Chem. Biol. 14:23–30 [Google Scholar]
  62. Kadakkuzha BM, Zhao L, Xia T. 62.  2009. Conformational distribution and ultrafast base dynamics of leadzyme. Biochemistry 48:3807–9 [Google Scholar]
  63. Manickam N, Nag N, Abbasi A, Patel K, Farabaugh PJ. 63.  2014. Studies of translational misreading in vivo show that the ribosome very efficiently discriminates against most potential errors. RNA 20:9–15 [Google Scholar]
  64. Stoddard CD, Widmann J, Trausch JJ, Marcano-Velázquez JG, Knight R, Batey RT. 64.  2013. Nucleotides adjacent to the ligand-binding pocket are linked to activity tuning in the purine riboswitch. J. Mol. Biol. 425:1596–611 [Google Scholar]
  65. Butcher SE, Dieckmann T, Feigon J. 65.  1997. Solution structure of a GAAA tetraloop receptor RNA. EMBO J. 16:7490–99 [Google Scholar]
  66. Shankar N, Kennedy SD, Chen G, Krugh TR, Turner DH. 66.  2006. The NMR structure of an internal loop from 23S ribosomal RNA differs from its structure in crystals of 50S ribosomal subunits. Biochemistry 45:11776–89 [Google Scholar]
  67. Schroeder SJ, Fountain MA, Kennedy SD, Lukavsky PJ, Puglisi JD. 67.  et al. 2003. Thermodynamic stability and structural features of the J4/5 loop in a Pneumocystis carinii group I intron. Biochemistry 42:14184–96 [Google Scholar]
  68. Rupert PB, Ferre-D'Amare AR. 68.  2001. Crystal structure of a hairpin ribozyme–inhibitor complex with implications for catalysis. Nature 410:780–86 [Google Scholar]
  69. Butcher SE, Allain FH, Feigon J. 69.  1999. Solution structure of the loop B domain from the hairpin ribozyme. Nat. Struct. Biol. 6:212–16 [Google Scholar]
  70. Cai Z, Tinoco I Jr. 70.  1996. Solution structure of loop A from the hairpin ribozyme from tobacco ringspot virus satellite. Biochemistry 35:6026–36 [Google Scholar]
  71. Cate JH, Gooding AR, Podell E, Zhou K, Golden BL. 71.  et al. 1996. Crystal structure of a group I ribozyme domain: principles of RNA packing. Science 273:1678–85 [Google Scholar]
  72. Lee JC, Gutell RR, Russell R. 72.  2006. The UAA/GAN internal loop motif: a new RNA structural element that forms a cross-strand AAA stack and long-range tertiary interactions. J. Mol. Biol. 360:978–88 [Google Scholar]
  73. Davis AR, Kirkpatrick CC, Znosko BM. 73.  2011. Structural characterization of naturally occurring RNA single mismatches. Nucleic Acids Res. 39:1081–94 [Google Scholar]
  74. Leontis NB, Stombaugh J, Westhof E. 74.  2002. The non–Watson–Crick base pairs and their associated isostericity matrices. Nucleic Acids Res. 30:3497–531 [Google Scholar]
  75. Gao XL, Patel DJ. 75.  1988. GSyn·AAnti mismatch formation in DNA dodecamers at acidic pH; pH-dependent conformational transition of G·A mispairs detected by proton NMR. J. Am. Chem. Soc. 110:5178–82 [Google Scholar]
  76. Burkard ME, Turner DH. 76.  2000. NMR structures of r(GCAGGCGUGC)2 and determinants of stability for single guanosine–guanosine base pairs. Biochemistry 39:11748–62 [Google Scholar]
  77. Yildirim I, Park H, Disney MD, Schatz GC. 77.  2013. A dynamic structural model of expanded RNA CAG repeats: a refined X-ray structure and computational investigations using molecular dynamics and umbrella sampling simulations. J. Am. Chem. Soc. 135:3528–38 [Google Scholar]
  78. Chen G, Kennedy SD, Qiao J, Krugh TR, Turner DH. 78.  2006. An alternating sheared AA pair and elements of stability for a single sheared purine–purine pair flanked by sheared GA pairs in RNA. Biochemistry 45:6889–903 [Google Scholar]
  79. Mathews DH, Case DA. 79.  2006. Nudged elastic band calculation of minimal energy paths for the conformational change of a GG non-canonical pair. J. Mol. Biol. 357:1683–93 [Google Scholar]
  80. Demeshkina N, Jenner L, Westhof E, Yusupov M, Yusupova G. 80.  2012. A new understanding of the decoding principle on the ribosome. Nature 484:256–59 [Google Scholar]
  81. Peterson RD, Feigon J. 81.  1996. Structural change in Rev responsive element RNA of HIV-1 on binding Rev peptide. J. Mol. Biol. 264:863–77 [Google Scholar]
  82. Schroeder KT, Lilley DM. 82.  2009. Ion-induced folding of a kink turn that departs from the conventional sequence. Nucleic Acids Res. 37:7281–89 [Google Scholar]
  83. Znosko BM, Kennedy SD, Wille PC, Krugh TR, Turner DH. 83.  2004. Structural features and thermodynamics of the J4/5 loop from the Candida albicans and Candida dubliniensis group I introns. Biochemistry 43:15822–37 [Google Scholar]
  84. Weixlbaumer A, Murphy FV 4th, Dziergowska A, Malkiewicz A, Vendeix FA. 84.  et al. 2007. Mechanism for expanding the decoding capacity of transfer RNAs by modification of uridines. Nat. Struct. Mol. Biol. 14:498–502 [Google Scholar]
  85. Vendeix FA, Murphy FV 4th, Cantara WA, Leszczynska G, Gustilo EM. 85.  et al. 2012. Human tRNALys3UUU is pre-structured by natural modifications for cognate and wobble codon binding through keto–enol tautomerism. J. Mol. Biol. 416:467–85 [Google Scholar]
  86. Cantara WA, Murphy FV 4th, Demirci H, Agris PF. 86.  2013. Expanded use of sense codons is regulated by modified cytidines in tRNA. Proc. Natl. Acad. Sci. USA 110:10964–69 [Google Scholar]
  87. Butcher SE, Pyle AM. 87.  2011. The molecular interactions that stabilize RNA tertiary structure: RNA motifs, patterns, and networks. Acc. Chem. Res. 44:1302–11 [Google Scholar]
  88. Wu M, Tinoco I Jr. 88.  1998. RNA folding causes secondary structure rearrangement. Proc. Natl. Acad. Sci. USA 95:11555–60 [Google Scholar]
  89. Koculi E, Cho SS, Desai R, Thirumalai D, Woodson SA. 89.  2012. Folding path of P5abc RNA involves direct coupling of secondary and tertiary structures. Nucleic Acids Res. 40:8011–20 [Google Scholar]
  90. Herschlag D.90.  1992. Evidence for processivity and two-step binding of the RNA substrate from studies of J1/2 mutants of the Tetrahymena ribozyme. Biochemistry 31:1386–99 [Google Scholar]
  91. Bevilacqua PC, Kierzek R, Johnson KA, Turner DH. 91.  1992. Dynamics of ribozyme binding of substrate revealed by fluorescence-detected stopped-flow methods. Science 258:1355–58 [Google Scholar]
  92. Zhuang X, Kim H, Pereira MJ, Babcock HP, Walter NG, Chu S. 92.  2002. Correlating structural dynamics and function in single ribozyme molecules. Science 296:1473–76 [Google Scholar]
  93. Marcia M, Pyle AM. 93.  2012. Visualizing group II intron catalysis through the stages of splicing. Cell 151:497–507 [Google Scholar]
  94. Harris DA, Rueda D, Walter NG. 94.  2002. Local conformational changes in the catalytic core of the trans-acting hepatitis delta virus ribozyme accompany catalysis. Biochemistry 41:12051–61 [Google Scholar]
  95. Lee TS, Giambasu G, Harris ME, York DM. 95.  2011. Characterization of the structure and dynamics of the HDV ribozyme at different stages along the reaction path. J. Phys. Chem. Lett. 2:2538–43 [Google Scholar]
  96. Ke A, Zhou K, Ding F, Cate JH, Doudna JA. 96.  2004. A conformational switch controls hepatitis delta virus ribozyme catalysis. Nature 429:201–5 [Google Scholar]
  97. Zhang Q, Kang M, Peterson RD, Feigon J. 97.  2011. Comparison of solution and crystal structures of preQ1 riboswitch reveals calcium-induced changes in conformation and dynamics. J. Am. Chem. Soc. 133:5190–93 [Google Scholar]
  98. Houck-Loomis B, Durney MA, Salguero C, Shankar N, Nagle JM. 98.  et al. 2011. An equilibrium-dependent retroviral mRNA switch regulates translational recoding. Nature 480:561–64 [Google Scholar]
  99. Solomatin SV, Greenfeld M, Chu S, Herschlag D. 99.  2010. Multiple native states reveal persistent ruggedness of an RNA folding landscape. Nature 463:681–84 [Google Scholar]
  100. Hyeon C, Lee J, Yoon J, Hohng S, Thirumalai D. 100.  2012. Hidden complexity in the isomerization dynamics of Holliday junctions. Nat. Chem. 4:907–14 [Google Scholar]
  101. Mortimer SA, Weeks KM. 101.  2009. C2′-endo nucleotides as molecular timers suggested by the folding of an RNA domain. Proc. Natl. Acad. Sci. USA 106:15622–27 [Google Scholar]
  102. Ogle JM, Murphy FV 4th, Tarry MJ, Ramakrishnan V. 102.  2002. Selection of tRNA by the ribosome requires a transition from an open to a closed form. Cell 111:721–32 [Google Scholar]
  103. Ogle JM, Brodersen DE, Clemons WM Jr, Tarry MJ, Carter AP, Ramakrishnan V. 103.  2001. Recognition of cognate transfer RNA by the 30S ribosomal subunit. Science 292:897–902 [Google Scholar]
  104. Fourmy D, Recht MI, Blanchard SC, Puglisi JD. 104.  1996. Structure of the A site of Escherichia coli 16S ribosomal RNA complexed with an aminoglycoside antibiotic. Science 274:1367–71 [Google Scholar]
  105. Schmeing TM, Voorhees RM, Kelley AC, Gao YG, Murphy FV 4th. 105.  et al. 2009. The crystal structure of the ribosome bound to EF-Tu and aminoacyl-tRNA. Science 326:688–94 [Google Scholar]
  106. Geggier P, Dave R, Feldman MB, Terry DS, Altman RB. 106.  et al. 2010. Conformational sampling of aminoacyl-tRNA during selection on the bacterial ribosome. J. Mol. Biol. 399:576–95 [Google Scholar]
  107. Blanchard SC, Gonzalez RL, Kim HD, Chu S, Puglisi JD. 107.  2004. tRNA selection and kinetic proofreading in translation. Nat. Struct. Mol. Biol. 11:1008–14 [Google Scholar]
  108. Gromadski KB, Daviter T, Rodnina MV. 108.  2006. A uniform response to mismatches in codon–anticodon complexes ensures ribosomal fidelity. Mol. Cell 21:369–77 [Google Scholar]
  109. Pape T, Wintermeyer W, Rodnina M. 109.  1999. Induced fit in initial selection and proofreading of aminoacyl-tRNA on the ribosome. EMBO J. 18:3800–7 [Google Scholar]
  110. Turner DH, Sugimoto N, Freier SM. 110.  1988. RNA structure prediction. Annu. Rev. Biophys. Biophys. Chem. 17:167–92 [Google Scholar]
  111. Bailor MH, Mustoe AM, Brooks CL III, Al-Hashimi HM. 111.  2011. Topological constraints: using RNA secondary structure to model 3D conformation, folding pathways, and dynamic adaptation. Curr. Opin. Struct. Biol. 21:296–305 [Google Scholar]
  112. Zhang Q, Sun X, Watt ED, Al-Hashimi HM. 112.  2006. Resolving the motional modes that code for RNA adaptation. Science 311:653–56 [Google Scholar]
  113. Zhang Q, Stelzer AC, Fisher CK, Al-Hashimi HM. 113.  2007. Visualizing spatially correlated dynamics that directs RNA conformational transitions. Nature 450:1263–67 [Google Scholar]
  114. Sun X, Zhang Q, Al-Hashimi HM. 114.  2007. Resolving fast and slow motions in the internal loop containing stem-loop 1 of HIV-1 that are modulated by Mg2+ binding: role in the kissing-duplex structural transition. Nucleic Acids Res. 35:1698–713 [Google Scholar]
  115. Bailor MH, Musselman C, Hansen AL, Gulati K, Patel DJ, Al-Hashimi HM. 115.  2007. Characterizing the relative orientation and dynamics of RNA A-form helices using NMR residual dipolar couplings. Nat. Protoc. 2:1536–46 [Google Scholar]
  116. Getz MM, Andrews AJ, Fierke CA, Al-Hashimi HM. 116.  2007. Structural plasticity and Mg2+ binding properties of RNase P P4 from combined analysis of NMR residual dipolar couplings and motionally decoupled spin relaxation. RNA 13:251–66 [Google Scholar]
  117. Olsen GL, Bardaro MF Jr, Echodu DC, Drobny GP, Varani G. 117.  2010. Intermediate rate atomic trajectories of RNA by solid-state NMR spectroscopy. J. Am. Chem. Soc. 132:303–8 [Google Scholar]
  118. Hohng S, Wilson TJ, Tan E, Clegg RM, Lilley DM, Ha T. 118.  2004. Conformational flexibility of four-way junctions in RNA. J. Mol. Biol. 336:69–79 [Google Scholar]
  119. Melcher SE, Wilson TJ, Lilley DM. 119.  2003. The dynamic nature of the four-way junction of the hepatitis C virus IRES. RNA 9:809–20 [Google Scholar]
  120. Reblova K, Sponer J, Lankas F. 120.  2012. Structure and mechanical properties of the ribosomal L1 stalk three-way junction. Nucleic Acids Res. 40:6290–303 [Google Scholar]
  121. Besseova I, Reblova K, Leontis NB, Sponer J. 121.  2010. Molecular dynamics simulations suggest that RNA three-way junctions can act as flexible RNA structural elements in the ribosome. Nucleic Acids Res. 38:6247–64 [Google Scholar]
  122. Grant GP, Boyd N, Herschlag D, Qin PZ. 122.  2009. Motions of the substrate recognition duplex in a group I intron assessed by site-directed spin labeling. J. Am. Chem. Soc. 131:3136–37 [Google Scholar]
  123. Zhang Q, Kim NK, Peterson RD, Wang Z, Feigon J. 123.  2010. Structurally conserved five nucleotide bulge determines the overall topology of the core domain of human telomerase RNA. Proc. Natl. Acad. Sci. USA 107:18761–68 [Google Scholar]
  124. Salmon L, Bascom G, Andricioaei I, Al-Hashimi HM. 124.  2013. A general method for constructing atomic-resolution RNA ensembles using NMR residual dipolar couplings: the basis for interhelical motions revealed. J. Am. Chem. Soc. 135:5457–66 [Google Scholar]
  125. Stelzer AC, Kratz JD, Zhang Q, Al-Hashimi HM. 125.  2010. RNA dynamics by design: biasing ensembles towards the ligand-bound state. Angew. Chem. Int. Ed. Engl. 49:5731–33 [Google Scholar]
  126. Casiano-Negroni A, Sun X, Al-Hashimi HM. 126.  2007. Probing Na+-induced changes in the HIV-1 TAR conformational dynamics using NMR residual dipolar couplings: new insights into the role of counterions and electrostatic interactions in adaptive recognition. Biochemistry 46:6525–35 [Google Scholar]
  127. Walter AE, Turner DH, Kim J, Lyttle MH, Müller P. 127.  et al. 1994. Coaxial stacking of helixes enhances binding of oligoribonucleotides and improves predictions of RNA folding. Proc. Natl. Acad. Sci. USA 91:9218–22 [Google Scholar]
  128. Tyagi R, Mathews DH. 128.  2007. Predicting helical coaxial stacking in RNA multibranch loops. RNA 13:939–51 [Google Scholar]
  129. Bailor MH, Sun X, Al-Hashimi HM. 129.  2010. Topology links RNA secondary structure with global conformation, dynamics, and adaptation. Science 327:202–6 [Google Scholar]
  130. Chu VB, Lipfert J, Bai Y, Pande VS, Doniach S, Herschlag D. 130.  2009. Do conformational biases of simple helical junctions influence RNA folding stability and specificity?. RNA 15:2195–205 [Google Scholar]
  131. Alexander RW, Eargle J, Luthey-Schulten Z. 131.  2010. Experimental and computational determination of tRNA dynamics. FEBS Lett. 584:376–86 [Google Scholar]
  132. Frank AT, Stelzer AC, Al-Hashimi HM, Andricioaei I. 132.  2009. Constructing RNA dynamical ensembles by combining MD and motionally decoupled NMR RDCs: new insights into RNA dynamics and adaptive ligand recognition. Nucleic Acids Res. 37:3670–79 [Google Scholar]
  133. Heppell B, Blouin S, Dussault AM, Mulhbacher J, Ennifar E. 133.  et al. 2011. Molecular insights into the ligand-controlled organization of the SAM-I riboswitch. Nat. Chem. Biol. 7:384–92 [Google Scholar]
  134. Haller A, Altman RB, Soulière MF, Blanchard SC, Micura R. 134.  2013. Folding and ligand recognition of the TPP riboswitch aptamer at single-molecule resolution. Proc. Natl. Acad. Sci. USA 110:4188–93 [Google Scholar]
  135. Fiegland LR, Garst AD, Batey RT, Nesbitt DJ. 135.  2012. Single-molecule studies of the lysine riboswitch reveal effector-dependent conformational dynamics of the aptamer domain. Biochemistry 51:9223–33 [Google Scholar]
  136. Stoddard CD, Montange RK, Hennelly SP, Rambo RP, Sanbonmatsu KY, Batey RT. 136.  2010. Free state conformational sampling of the SAM-I riboswitch aptamer domain. Structure 18:787–97 [Google Scholar]
  137. Baird NJ, Ferre-D'Amare AR. 137.  2010. Idiosyncratically tuned switching behavior of riboswitch aptamer domains revealed by comparative small-angle X-ray scattering analysis. RNA 16:598–609 [Google Scholar]
  138. Brenner MD, Scanlan MS, Nahas MK, Ha T, Silverman SK. 138.  2010. Multivector fluorescence analysis of the xpt guanine riboswitch aptamer domain and the conformational role of guanine. Biochemistry 49:1596–605 [Google Scholar]
  139. Lipfert J, Das R, Chu VB, Kudaravalli M, Boyd N. 139.  et al. 2007. Structural transitions and thermodynamics of a glycine-dependent riboswitch from Vibrio cholerae. J. Mol. Biol. 365:1393–406 [Google Scholar]
  140. Mulder AM, Yoshioka C, Beck AH, Bunner AE, Milligan RA. 140.  et al. 2010. Visualizing ribosome biogenesis: parallel assembly pathways for the 30S subunit. Science 330:673–77 [Google Scholar]
  141. Adilakshmi T, Bellur DL, Woodson SA. 141.  2008. Concurrent nucleation of 16S folding and induced fit in 30S ribosome assembly. Nature 455:1268–72 [Google Scholar]
  142. Menichelli E, Isel C, Oubridge C, Nagai K. 142.  2007. Protein-induced conformational changes of RNA during the assembly of human signal recognition particle. J. Mol. Biol. 367:187–203 [Google Scholar]
  143. Stone MD, Mihalusova M, O'Connor CM, Prathapam R, Collins K, Zhuang X. 143.  2007. Stepwise protein-mediated RNA folding directs assembly of telomerase ribonucleoprotein. Nature 446:458–61 [Google Scholar]
  144. Chen J, Tsai A, O'Leary SE, Petrov A, Puglisi JD. 144.  2012. Unraveling the dynamics of ribosome translocation. Curr. Opin. Struct. Biol. 22:804–14 [Google Scholar]
  145. Frank J, Gonzalez RL Jr. 145.  2010. Structure and dynamics of a processive Brownian motor: the translating ribosome. Annu. Rev. Biochem. 79:381–412 [Google Scholar]
  146. Ratje AH, Loerke J, Mikolajka A, Brunner M, Hildebrand PW. 146.  et al. 2010. Head swivel on the ribosome facilitates translocation by means of intra-subunit tRNA hybrid sites. Nature 468:713–16 [Google Scholar]
  147. Fischer N, Konevega AL, Wintermeyer W, Rodnina MV, Stark H. 147.  2010. Ribosome dynamics and tRNA movement by time-resolved electron cryomicroscopy. Nature 466:329–33 [Google Scholar]
  148. Valle M, Zavialov A, Sengupta J, Rawat U, Ehrenberg M, Frank J. 148.  2003. Locking and unlocking of ribosomal motions. Cell 114:123–34 [Google Scholar]
  149. Zhang W, Dunkle JA, Cate JH. 149.  2009. Structures of the ribosome in intermediate states of ratcheting. Science 325:1014–17 [Google Scholar]
  150. Dunkle JA, Wang L, Feldman MB, Pulk A, Chen VB. 150.  et al. 2011. Structures of the bacterial ribosome in classical and hybrid states of tRNA binding. Science 332:981–84 [Google Scholar]
  151. Tama F, Valle M, Frank J, Brooks CL III. 151.  2003. Dynamic reorganization of the functionally active ribosome explored by normal mode analysis and cryo-electron microscopy. Proc. Natl. Acad. Sci. USA 100:9319–23 [Google Scholar]
  152. Fei J, Kosuri P, MacDougall DD, Gonzalez RL Jr. 152.  2008. Coupling of ribosomal L1 stalk and tRNA dynamics during translation elongation. Mol. Cell 30:348–59 [Google Scholar]
  153. Fei J, Bronson JE, Hofman JM, Srinivas RL, Wiggins CH, Gonzalez RL Jr. 153.  2009. Allosteric collaboration between elongation factor G and the ribosomal L1 stalk directs tRNA movements during translation. Proc. Natl. Acad. Sci. USA 106:15702–7 [Google Scholar]
  154. Cornish PV, Ermolenko DN, Staple DW, Hoang L, Hickerson RP. 154.  et al. 2009. Following movement of the L1 stalk between three functional states in single ribosomes. Proc. Natl. Acad. Sci. USA 106:2571–76 [Google Scholar]
  155. Tsai A, Uemura S, Johansson M, Puglisi EV, Marshall RA. 155.  et al. 2013. The impact of aminoglycosides on the dynamics of translation elongation. Cell Rep. 3:497–508 [Google Scholar]
  156. Wang L, Pulk A, Wasserman MR, Feldman MB, Altman RB. 156.  et al. 2012. Allosteric control of the ribosome by small-molecule antibiotics. Nat. Struct. Mol. Biol. 19:957–63 [Google Scholar]
  157. Ermolenko DN, Spiegel PC, Majumdar ZK, Hickerson RP, Clegg RM, Noller HF. 157.  2007. The antibiotic viomycin traps the ribosome in an intermediate state of translocation. Nat. Struct. Mol. Biol. 14:493–97 [Google Scholar]
  158. Menger M, Eckstein F, Porschke D. 158.  2000. Dynamics of the RNA hairpin GNRA tetraloop. Biochemistry 39:4500–7 [Google Scholar]
  159. Johnson JE Jr, Hoogstraten CG. 159.  2008. Extensive backbone dynamics in the GCAA RNA tetraloop analyzed using 13C NMR spin relaxation and specific isotope labeling. J. Am. Chem. Soc. 130:16757–69 [Google Scholar]
  160. Zhao L, Xia T. 160.  2007. Direct revelation of multiple conformations in RNA by femtosecond dynamics. J. Am. Chem. Soc. 129:4118–19 [Google Scholar]
  161. DePaul AJ, Thompson EJ, Patel SS, Haldeman K, Sorin EJ. 161.  2010. Equilibrium conformational dynamics in an RNA tetraloop from massively parallel molecular dynamics. Nucleic Acids Res. 38:4856–67 [Google Scholar]
  162. Jucker FM, Heus HA, Yip PF, Moors EH, Pardi A. 162.  1996. A network of heterogeneous hydrogen bonds in GNRA tetraloops. J. Mol. Biol. 264:968–80 [Google Scholar]
  163. Zhang YF, Zhao X, Mu YG. 163.  2009. Conformational transition map of an RNA GCAA tetraloop explored by replica-exchange molecular dynamics simulation. J. Chem. Theory Comput. 5:1146–54 [Google Scholar]
  164. Goh GB, Knight JL, Brooks CL III. 164.  2013. pH-dependent dynamics of complex RNA macromolecules. J. Chem. Theory Comput. 9:935–43 [Google Scholar]
  165. Leulliot N, Varani G. 165.  2001. Current topics in RNA–protein recognition: control of specificity and biological function through induced fit and conformational capture. Biochemistry 40:7947–56 [Google Scholar]
  166. Xia T.166.  2008. Taking femtosecond snapshots of RNA conformational dynamics and complexity. Curr. Opin. Chem. Biol. 12:604–11 [Google Scholar]
  167. Hermann T, Patel DJ. 167.  2000. Adaptive recognition by nucleic acid aptamers. Science 287:820–25 [Google Scholar]
  168. Tan D, Marzluff WF, Dominski Z, Tong L. 168.  2013. Structure of histone mRNA stem-loop, human stem-loop binding protein, and 3′hExo ternary complex. Science 339:318–21 [Google Scholar]
  169. Stelzer AC, Frank AT, Kratz JD, Swanson MD, Gonzalez-Hernandez MJ. 169.  et al. 2011. Discovery of selective bioactive small molecules by targeting an RNA dynamic ensemble. Nat. Chem. Biol. 7:553–59 [Google Scholar]
  170. Woodson SA.170.  2010. Compact intermediates in RNA folding. Annu. Rev. Biophys. 39:61–77 [Google Scholar]
  171. Frieda KL, Block SM. 171.  2012. Direct observation of cotranscriptional folding in an adenine riboswitch. Science 338:397–400 [Google Scholar]
  172. Duncan CD, Weeks KM. 172.  2010. Nonhierarchical ribonucleoprotein assembly suggests a strain-propagation model for protein-facilitated RNA folding. Biochemistry 49:5418–25 [Google Scholar]
  173. Stern S, Changchien LM, Craven GR, Noller HF. 173.  1988. Interaction of proteins S16, S17 and S20 with 16S ribosomal RNA. J. Mol. Biol. 200:291–99 [Google Scholar]
  174. Ramaswamy P, Woodson SA. 174.  2009. S16 throws a conformational switch during assembly of 30S 5′ domain. Nat. Struct. Mol. Biol. 16:438–45 [Google Scholar]
  175. Whitford PC, Geggier P, Altman RB, Blanchard SC, Onuchic JN, Sanbonmatsu KY. 175.  2010. Accommodation of aminoacyl-tRNA into the ribosome involves reversible excursions along multiple pathways. RNA 16:1196–204 [Google Scholar]
  176. Eichhorn CD, Feng J, Suddala KC, Walter NG, Brooks CL III, Al-Hashimi HM. 176.  2012. Unraveling the structural complexity in a single-stranded RNA tail: implications for efficient ligand binding in the prequeuosine riboswitch. Nucleic Acids Res. 40:1345–55 [Google Scholar]
  177. Suddala KC, Rinaldi AJ, Feng J, Mustoe AM, Eichhorn CD. 177.  et al. 2013. Single transcriptional and translational preQ1 riboswitches adopt similar pre-folded ensembles that follow distinct folding pathways into the same ligand-bound structure. Nucleic Acids Res. 41:10462–75 [Google Scholar]
  178. Sim AY, Levitt M. 178.  2011. Clustering to identify RNA conformations constrained by secondary structure. Proc. Natl. Acad. Sci. USA 108:3590–95 [Google Scholar]
  179. Nissen P, Ippolito JA, Ban N, Moore PB, Steitz TA. 179.  2001. RNA tertiary interactions in the large ribosomal subunit: the A-minor motif. Proc. Natl. Acad. Sci. USA 98:4899–903 [Google Scholar]
  180. Doherty EA, Batey RT, Masquida B, Doudna JA. 180.  2001. A universal mode of helix packing in RNA. Nat. Struct. Biol. 8:339–43 [Google Scholar]
  181. Sattin BD, Zhao W, Travers K, Chu S, Herschlag D. 181.  2008. Direct measurement of tertiary contact cooperativity in RNA folding. J. Am. Chem. Soc. 130:6085–87 [Google Scholar]
  182. Behrouzi R, Roh JH, Kilburn D, Briber RM, Woodson SA. 182.  2012. Cooperative tertiary interaction network guides RNA folding. Cell 149:348–57 [Google Scholar]
  183. Das R, Travers KJ, Bai Y, Herschlag D. 183.  2005. Determining the Mg2+ stoichiometry for folding an RNA metal ion core. J. Am. Chem. Soc. 127:8272–73 [Google Scholar]
  184. Mustoe AM, Al-Hashimi HM, Brooks CL III. 184.  2014. Coarse grained models reveal essential contributions of topological constraints to the conformational free energy of RNA bulges. J. Phys. Chem. B. In press

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