Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Functional complexity and regulation through RNA dynamics

Abstract

Changes to the conformation of coding and non-coding RNAs form the basis of elements of genetic regulation and provide an important source of complexity, which drives many of the fundamental processes of life. Although the structure of RNA is highly flexible, the underlying dynamics of RNA are robust and are limited to transitions between the few conformations that preserve favourable base-pairing and stacking interactions. The mechanisms by which cellular processes harness the intrinsic dynamic behaviour of RNA and use it within functionally productive pathways are complex. The versatile functions and ease by which it is integrated into a wide variety of genetic circuits and biochemical pathways suggests there is a general and fundamental role for RNA dynamics in cellular processes.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Shape and form of RNA dynamics.
Figure 2: Triggering RNA conformational transitions.
Figure 3: Functional outputs of secondary structural changes.
Figure 4: Functional outputs of tertiary conformational changes.

Similar content being viewed by others

References

  1. Kendrew, J. C. et al. A three-dimensional model of the myoglobin molecule obtained by X-ray analysis. Nature 181, 662–666 (1958).

    Article  ADS  CAS  PubMed  Google Scholar 

  2. Rould, M. A., Perona, J. J., Söll, D. & Steitz, T. A. Structure of E. coli glutaminyl-tRNA synthetase complexed with tRNA(Gln) and ATP at 2.8 Å resolution. Science 246, 1135–1142 (1989).

    Article  ADS  CAS  PubMed  Google Scholar 

  3. Pley, H. W., Flaherty, K. M. & McKay, D. B. Three-dimensional structure of a hammerhead ribozyme. Nature 372, 68–74 (1994).

    Article  ADS  CAS  PubMed  Google Scholar 

  4. Scott, W. G., Finch, J. T. & Klug, A. The crystal structure of an all-RNA hammerhead ribozyme: a proposed mechanism for RNA catalytic cleavage. Cell 81, 991–1002 (1995).

    Article  CAS  PubMed  Google Scholar 

  5. Wang, S., Karbstein, K., Peracchi, A., Beigelman, L. & Herschlag, D. Identification of the hammerhead ribozyme metal ion binding site responsible for rescue of the deleterious effect of a cleavage site phosphorothioate. Biochemistry 38, 14363–14378 (1999).

    Article  CAS  PubMed  Google Scholar 

  6. Boehr, D. D., Nussinov, R. & Wright, P. E. The role of dynamic conformational ensembles in biomolecular recognition. Nature Chem. Biol. 5, 789–796 (2009).

    Article  CAS  Google Scholar 

  7. Al-Hashimi, H. M. & Walter, N. G. RNA dynamics: it is about time. Curr. Opin. Struct. Biol. 18, 321–329 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Frauenfelder, H., Sligar, S. G. & Wolynes, P. G. The energy landscapes and motions of proteins. Science 254, 1598–1603 (1991).

    Article  ADS  CAS  PubMed  Google Scholar 

  9. Cruz, J. A. & Westhof, E. The dynamic landscapes of RNA architecture. Cell 136, 604–609 (2009).

    Article  CAS  PubMed  Google Scholar 

  10. Bailor, M. H., Mustoe, A. M., Brooks, C. L. 3rd & Al-Hashimi, H. M. Topological constraints: using RNA secondary structure to model 3D conformation, folding pathways, and dynamic adaptation. Curr. Opin. Struct. Biol. 21, 296–305 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Schultes, E. A., Spasic, A., Mohanty, U. & Bartel, D. P. Compact and ordered collapse of randomly generated RNA sequences. Nature Struct. Mol. Biol. 12, 1130–1136 (2005).

    Article  CAS  Google Scholar 

  12. Schultes, E. A., Hraber, P. T. & LaBean, T. H. Estimating the contributions of selection and self-organization in RNA secondary structure. J. Mol. Evol. 49, 76–83 (1999).

    Article  ADS  CAS  PubMed  Google Scholar 

  13. Fürtig, B., Wenter, P., Pitsch, S. & Schwalbe, H. Probing mechanism and transition state of RNA refolding. ACS Chem. Biol. 5, 753–765 (2010).

    Article  PubMed  CAS  Google Scholar 

  14. Bailor, M. H., Sun, X. & Al-Hashimi, H. M. Topology links RNA secondary structure with global conformation, dynamics, and adaptation. Science 327, 202–206 (2010). This article reports the simple topological constraints that are governed by steric and stereochemical forces severely restrict the allowed orientation of helices across two-way junctions.

    Article  ADS  CAS  PubMed  Google Scholar 

  15. Mustoe, A. M., Bailor, M. H., Teixeira, R. M., Brooks, C. L. 3rd & Al-Hashimi, H. M. New insights into the fundamental role of topological constraints as a determinant of two-way junction conformation. Nucleic Acids Res. 40, 892–904 (2012).

    Article  CAS  PubMed  Google Scholar 

  16. Chu, V. B. et al. Do conformational biases of simple helical junctions influence RNA folding stability and specificity? RNA 15, 2195–2205 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Venditti, V., Clos, L. 2nd, Niccolai, N. & Butcher, S. E. Minimum-energy path for a U6 RNA conformational change involving protonation, base-pair rearrangement and base flipping. J. Mol. Biol. 391, 894–905 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Fourmy, D., Yoshizawa, S. & Puglisi, J. D. Paromomycin binding induces a local conformational change in the A-site of 16S rRNA. J. Mol. Biol. 277, 333–345 (1998).

    Article  CAS  PubMed  Google Scholar 

  19. Le, S. Y., Zhang, K. & Maizel, J. V. Jr. RNA molecules with structure dependent functions are uniquely folded. Nucleic Acids Res. 30, 3574–3582 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Stelzer, A. C., Kratz, J. D., Zhang, Q. & Al-Hashimi, H. M. RNA dynamics by design: biasing ensembles towards the ligand-bound state. Angew. Chem. Int. Ed. Engl. 49, 5731–5733 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Shankar, N. et al. NMR reveals the absence of hydrogen bonding in adjacent UU and AG mismatches in an isolated internal loop from ribosomal RNA. Biochemistry 46, 12665–12678 (2007).

    Article  CAS  PubMed  Google Scholar 

  22. Frank, J. & Gonzalez, R. L., Jr. Structure and dynamics of a processive Brownian motor: the translating ribosome. Annu. Rev. Biochem. 79, 381–412 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Haller, A., Souliere, M. F. & Micura, R. The dynamic nature of RNA as key to understanding riboswitch mechanisms. Acc. Chem. Res. 44, 1339–1348 (2011).

    Article  CAS  PubMed  Google Scholar 

  24. Paukstelis, P. J., Chen, J. H., Chase, E., Lambowitz, A. M. & Golden, B. L. Structure of a tyrosyl-tRNA synthetase splicing factor bound to a group I intron RNA. Nature 451, 94–97 (2008).

    Article  ADS  CAS  PubMed  Google Scholar 

  25. Puglisi, J. D., Tan, R., Calnan, B. J., Frankel, A. D. & Williamson, J. R. Conformation of the TAR RNA-arginine complex by NMR spectroscopy. Science 257, 76–80 (1992).

    Article  ADS  CAS  PubMed  Google Scholar 

  26. Orr, J. W., Hagerman, P. J. & Williamson, J. R. Protein and Mg2+-induced conformational changes in the S15 binding site of 16S ribosomal RNA. J. Mol. Biol. 275, 453–464 (1998).

    Article  CAS  PubMed  Google Scholar 

  27. Turner, B., Melcher, S. E., Wilson, T. J., Norman, D. G. & Lilley, D. M. Induced fit of RNA on binding the L7Ae protein to the kink-turn motif. RNA 11, 1192–1200 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Falb, M., Amata, I., Gabel, F., Simon, B. & Carlomagno, T. Structure of the K-turn U4 RNA: a combined NMR and SANS study. Nucleic Acids Res. 38, 6274–6285 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Kim, H. D. et al. Mg2+-dependent conformational change of RNA studied by fluorescence correlation and FRET on immobilized single molecules. Proc. Natl Acad. Sci. USA 99, 4284–4289 (2002).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  30. Zacharias, M. & Hagerman, P. J. The influence of symmetric internal loops on the flexibility of RNA. J. Mol. Biol. 257, 276–289 (1996).

    Article  CAS  PubMed  Google Scholar 

  31. Zhang, Q., Stelzer, A. C., Fisher, C. K. & Al-Hashimi, H. M. Visualizing spatially correlated dynamics that directs RNA conformational transitions. Nature 450, 1263–1267 (2007).

    Article  ADS  CAS  PubMed  Google Scholar 

  32. Shajani, Z., Drobny, G. & Varani, G. Binding of U1A protein changes RNA dynamics as observed by 13C NMR relaxation studies. Biochemistry 46, 5875–5883 (2007).

    Article  CAS  PubMed  Google Scholar 

  33. Bokinsky, G. et al. Two distinct binding modes of a protein cofactor with its target RNA. J. Mol. Biol. 361, 771–784 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Bardaro, M. F. Jr., Shajani, Z., Patora-Komisarska, K., Robinson, J. A. & Varani, G. How binding of small molecule and peptide ligands to HIV-1 TAR alters the RNA motional landscape. Nucleic Acids Res. 37, 1529–1540 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Herschlag, D., Khosla, M., Tsuchihashi, Z. & Karpel, R. L. An RNA chaperone activity of non-specific RNA binding proteins in hammerhead ribozyme catalysis. EMBO J. 13, 2913–2924 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Pyle, A. M. & Green, J. B. RNA folding. Curr. Opin. Struct. Biol. 5, 303–310 (1995).

    Article  CAS  PubMed  Google Scholar 

  37. Treiber, D.K. & Williamson, J.R. Beyond kinetic traps in RNA folding. Curr. Opin. Struct. Biol. 11, 309–314 (2001).

    Article  CAS  PubMed  Google Scholar 

  38. Hirling, H., Scheffner, M., Restle, T. & Stahl, H. RNA helicase activity associated with the human p68 protein. Nature 339, 562–564 (1989).

    Article  ADS  CAS  PubMed  Google Scholar 

  39. Yang, Q. & Jankowsky, E. ATP- and ADP-dependent modulation of RNA unwinding and strand annealing activities by the DEAD-box protein DED1. Biochemistry 44, 13591–13601 (2005).

    Article  CAS  PubMed  Google Scholar 

  40. Will, C. L. & Lührmann, R. Spliceosome structure and function. Cold Spring Harb. Perspect. Biol. 3, a003707 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Kosowski, T. R., Keys, H. R., Quan, T. K. & Ruby, S. W. DExD/H-box Prp5 protein is in the spliceosome during most of the splicing cycle. RNA 15, 1345–1362 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Maeder, C., Kutach, A. K. & Guthrie, C. ATP-dependent unwinding of U4/U6 snRNAs by the Brr2 helicase requires the C terminus of Prp8. Nature Struct. Mol. Biol. 16, 42–48 (2009).

    Article  CAS  Google Scholar 

  43. Schwer, B. A conformational rearrangement in the spliceosome sets the stage for Prp22-dependent mRNA release. Mol. Cell 30, 743–754 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Bhaskaran, H. & Russell, R. Kinetic redistribution of native and misfolded RNAs by a DEAD-box chaperone. Nature 449, 1014–1018 (2007).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  45. Winkler, W., Nahvi, A. & Breaker, R. R. Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expression. Nature 419, 952–956 (2002). This article reports the discovery of an RNA switch in the 5′ untranslated region of bacterial mRNA that regulates gene expression in response to ligands without assistance from proteins.

    Article  ADS  CAS  PubMed  Google Scholar 

  46. Cromie, M. J., Shi, Y., Latifi, T. & Groisman, E. A. An RNA sensor for intracellular Mg2+. Cell 125, 71–84 (2006).

    Article  CAS  PubMed  Google Scholar 

  47. Nechooshtan, G., Elgrably-Weiss, M., Sheaffer, A., Westhof, E. & Altuvia, S. A pH-responsive riboregulator. Genes Dev. 23, 2650–2662 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Greenleaf, W. J., Frieda, K. L., Foster, D. A. Woodside, M. T. & Block, S. M. Direct observation of hierarchical folding in single riboswitch aptamers. Science 319, 630–633 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Mandal, M. et al. A glycine-dependent riboswitch that uses cooperative binding to control gene expression. Science 306, 275–279 (2004).

    Article  ADS  CAS  PubMed  Google Scholar 

  50. Sudarsan, N. et al. Tandem riboswitch architectures exhibit complex gene control functions. Science 314, 300–304 (2006).

    Article  ADS  CAS  PubMed  Google Scholar 

  51. Lee, E. R., Baker, J. L., Weinberg, Z., Sudarsan, N. & Breaker, R. R. An allosteric self-splicing ribozyme triggered by a bacterial second messenger. Science 329, 845–848 (2010).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  52. Ferre-D'Amare, A. R., Zhou, K. & Doudna, J. A. Crystal structure of a hepatitis delta virus ribozyme. Nature 395, 567–574 (1998).

    Article  ADS  CAS  PubMed  Google Scholar 

  53. Ke, A., Zhou, K., Ding, F., Cate, J. H. D. & Doudna, J. A. A conformational switch controls hepatitis delta virus ribozyme catalysis. Nature 429, 201–205 (2004). This article reports a significant local conformational change in the active site of the HDV ribozyme is observed post-cleavage and is associated with ejection of the substrate and a catalytically critical divalent metal ion.

    Article  ADS  CAS  PubMed  Google Scholar 

  54. Harris, D. A., Rueda, D. & Walter, N. G. Local conformational changes in the catalytic core of the trans-acting hepatitis delta virus ribozyme accompany catalysis. Biochemistry 41, 12051–12061 (2002).

    Article  CAS  PubMed  Google Scholar 

  55. Lamanna, A. C. & Karbstein, K. An RNA conformational switch regulates pre-18S rRNA cleavage. J. Mol. Biol. 405, 3–17 (2011).

    Article  CAS  PubMed  Google Scholar 

  56. Nocker, A. et al. A mRNA-based thermosensor controls expression of rhizobial heat shock genes. Nucleic Acids Res. 29, 4800–4807 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Johansson, J. et al. An RNA thermosensor controls expression of virulence genes in Listeria monocytogenes. Cell 110, 551–561 (2002).

    Article  PubMed  Google Scholar 

  58. Watts, J. M. et al. Architecture and secondary structure of an entire HIV-1 RNA genome. Nature 460, 711–716 (2009).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  59. Grundy, F. J., Winkler, W. C. & Henkin, T. M. tRNA-mediated transcription antitermination in vitro: codon-anticodon pairing independent of the ribosome. Proc. Natl Acad. Sci. USA 99, 11121–11126 (2002).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  60. Babitzke, P. & Yanofsky, C. Reconstitution of Bacillus subtilis trp attenuation in vitro with TRAP, the trp RNA-binding attenuation protein. Proc. Natl Acad. Sci. USA 90, 133–137 (1993).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  61. Diaz-Toledano, R., Ariza-Mateos, A., Birk, A., Martinez-Garcia, B. & Gomez, J. In vitro characterization of a miR-122-sensitive double-helical switch element in the 5´ region of hepatitis C virus RNA. Nucleic Acids Res. 37, 5498–5510 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Ray, P. S. et al. A stress-responsive RNA switch regulates VEGFA expression. Nature 457, 915–919 (2009). This article reports that the 3′ untranslated region of human VEGFA mRNA undergoes a binary conformational switch in response to inflammatory and hypoxic protein stress signals to regulate VEGFA expression.

    Article  ADS  CAS  PubMed  Google Scholar 

  63. Cheah, M. T., Wachter, A., Sudarsan, N. & Breaker, R. R. Control of alternative RNA splicing and gene expression by eukaryotic riboswitches. Nature 447, 497–500 (2007). This article reports a secondary structural change in a eukaryotic thiamine pyrophosphate riboswitch regulates gene expression through the control of alternative splicing.

    Article  ADS  CAS  PubMed  Google Scholar 

  64. Kedde, M. et al. A Pumilio-induced RNA structure switch in p27-3′ untranslated region controls miR-221 and miR-222 accessibility. Nature Cell Biol. 12, 1014–1020 (2010).

    Article  CAS  PubMed  Google Scholar 

  65. Casey, J. L. Control of ADAR1 editing of hepatitis delta virus RNAs. Curr. Top. Microbiol. Immunol. 353, 123–143 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Abbink, T. E., Ooms, M., Haasnoot, P. C. & Berkhout, B. The HIV-1 leader RNA conformational switch regulates RNA dimerization but does not regulate mRNA translation. Biochemistry 44, 9058–9066 (2005).

    Article  CAS  PubMed  Google Scholar 

  67. Miyazaki, Y. et al. An RNA structural switch regulates diploid genome packaging by Moloney murine leukemia virus. J. Mol. Biol. 396, 141–152 (2010). This article reports that dimerization of the 5′ untranslated region of the Moloney murine leukaemia virus results in a secondary structural change that promotes genome packaging.

    Article  CAS  PubMed  Google Scholar 

  68. Giege, R. Toward a more complete view of tRNA biology. Nature Struct. Mol. Biol. 15, 1007–1014 (2008).

    Article  CAS  Google Scholar 

  69. Mulder, A. M. et al. Visualizing ribosome biogenesis: parallel assembly pathways for the 30S subunit. Science 330, 673–677 (2010).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  70. Adilakshmi, T., Bellur, D. L. & Woodson, S. A. Concurrent nucleation of 16S folding and induced fit in 30S ribosome assembly. Nature 455, 1268–1272 (2008).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  71. Menichelli, E., Isel, C., Oubridge, C. & Nagai, K. Protein-induced conformational changes of RNA during the assembly of human signal recognition particle. J. Mol. Biol. 367, 187–203 (2007).

    Article  CAS  PubMed  Google Scholar 

  72. Stone, M. D. et al. Stepwise protein-mediated RNA folding directs assembly of telomerase ribonucleoprotein. Nature 446, 458–461 (2007).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  73. Held, W. A., Ballou, B., Mizushima, S. & Nomura, M. Assembly mapping of 30S ribosomal proteins from Escherichia coli. Further studies. J. Biol. Chem. 249, 3103–3111 (1974).

    Article  CAS  PubMed  Google Scholar 

  74. Agalarov, S. C., Prasad, G. S., Funke, P. M., Stout, C. D. & Williamson, J. R. Structure of the S15,S6,S18-rRNA complex: assembly of the 30S ribosome central domain. Science 288, 107–112 (2000).

    Article  ADS  CAS  PubMed  Google Scholar 

  75. Duncan, C. D. & Weeks, K. M. Nonhierarchical ribonucleoprotein assembly suggests a strain-propagation model for protein-facilitated RNA folding. Biochemistry 49, 5418–5425 (2010).

    Article  CAS  PubMed  Google Scholar 

  76. Wilson, T. J., Nahas, M., Ha, T. & Lilley, D. M. Folding and catalysis of the hairpin ribozyme. Biochem. Soc. Trans. 33, 461–465 (2005).

    Article  CAS  PubMed  Google Scholar 

  77. Zhang, Q., Kim, N. K., Peterson, R. D., Wang, Z. & Feigon, J. Structurally conserved five nucleotide bulge determines the overall topology of the core domain of human telomerase RNA. Proc. Natl Acad. Sci. USA 107, 18761–18768 (2010).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  78. Solomatin, S. V., Greenfeld, M., Chu, S. & Herschlag, D. Multiple native states reveal persistent ruggedness of an RNA folding landscape. Nature 463, 681–684 (2010). This article reports the observation of slowly interconverting catalytically active states in a ribozyme, thereby establishing the coexistence of multiple native states.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  79. Greenfeld, M., Solomatin, S. V. & Herschlag, D. Removal of covalent heterogeneity reveals simple folding behavior for P4–P6 RNA. J. Biol. Chem. 286, 19872–19879 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Frank, J. & Agrawal, R. K. A ratchet-like inter-subunit reorganization of the ribosome during translocation. Nature 406, 318–322 (2000).

    Article  ADS  CAS  PubMed  Google Scholar 

  81. Valle, M. et al. Locking and unlocking of ribosomal motions. Cell 114, 123–134 (2003).

    Article  CAS  PubMed  Google Scholar 

  82. Zhang, W., Dunkle, J. A. & Cate, J. H. Structures of the ribosome in intermediate states of ratcheting. Science 325, 1014–1017 (2009).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  83. Ratje, A. H. et al. Head swivel on the ribosome facilitates translocation by means of intra-subunit tRNA hybrid sites. Nature 468, 713–716 (2010).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  84. Fischer, N., Konevega, A. L. Wintermeyer, W., Rodnina, M. V. & Stark, H. Ribosome dynamics and tRNA movement by time-resolved electron cryomicroscopy. Nature 466, 329–333 (2010). This article demonstrates the cryo-electron microscopy observation of thermally driven tRNA retrotranslocation on the ribosome.

    Article  ADS  CAS  PubMed  Google Scholar 

  85. Shoji, S., Walker, S. E. & Fredrick, K. Reverse translocation of tRNA in the ribosome. Mol. Cell 24, 931–942 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Ogle, J. M., Murphy, F. V., Tarry, M. J. & Ramakrishnan, V. Selection of tRNA by the ribosome requires a transition from an open to a closed form. Cell 111, 721–732 (2002).

    Article  CAS  PubMed  Google Scholar 

  87. Valle, M. et al. Incorporation of aminoacyl-tRNA into the ribosome as seen by cryo-electron microscopy. Nature Struct. Biol. 10, 899–906 (2003).

    Article  CAS  PubMed  Google Scholar 

  88. Lee, T. H., Blanchard, S. C., Kim, H. D., Puglisi, J. D. & Chu, S. The role of fluctuations in tRNA selection by the ribosome. Proc. Natl Acad. Sci. USA 104, 13661–13665 (2007).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  89. Schmeing, T. M. et al. The crystal structure of the ribosome bound to EF-Tu and aminoacyl-tRNA. Science 326, 688–694 (2009).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  90. Voorhees, R. M., Schmeing, T. M., Kelley, A. C. & Ramakrishnan, V. The mechanism for activation of GTP hydrolysis on the ribosome. Science 330, 835–838 (2010).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  91. Pape, T., Wintermeyer, W. & Rodnina, M. V. Conformational switch in the decoding region of 16S rRNA during aminoacyl-tRNA selection on the ribosome. Nature Struct. Mol. Biol. 7, 104–107 (2000).

    Article  CAS  Google Scholar 

  92. Blanchard, S. C., Gonzalez, R. L., Kim, H. D., Chu, S. & Puglisi, J. D. tRNA selection and kinetic proofreading in translation. Nature Struct. Mol. Biol. 11, 1008–1014 (2004). This important single-molecule FRET study directly observes the dynamics of tRNA initial selection and proofreading by the ribosome.

    Article  CAS  Google Scholar 

  93. Fei, J. et al., Allosteric collaboration between elongation factor G and the ribosomal L1 stalk directs tRNA movements during translation. Proc. Natl Acad. Sci. USA 106, 15702–15707 (2009).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  94. Blaha, G., Stanley, R. E. & Steitz, T. A. Formation of the first peptide bond: the structure of EF-P bound to the 70S ribosome. Science 325, 966–970 (2009).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  95. Dunkle, J. A. et al. Structures of the bacterial ribosome in classical and hybrid states of tRNA binding. Science 332, 981–984 (2011).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  96. Laurberg, M. et al. Structural basis for translation termination on the 70S ribosome. Nature 454, 852–857 (2008).

    Article  ADS  CAS  PubMed  Google Scholar 

  97. Cornish, P. V., Ermolenko, D. N., Noller, H. F. & Ha, T. Spontaneous intersubunit rotation in single ribosomes. Mol. Cell 30, 578–588 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Tama, F., Valle, M., Frank, J. & Brooks, C. L 3rd. Dynamic reorganization of the functionally active ribosome explored by normal mode analysis and cryo-electron microscopy. Proc. Natl Acad. Sci. USA 100, 9319–9323 (2003).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  99. Green, N. J., Grundy, F. J. & Henkin, T. M. The T box mechanism: tRNA as a regulatory molecule. FEBS Lett. 584, 318–324 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Cornish, P. V. et al. Following movement of the L1 stalk between three functional states in single ribosomes. Proc. Natl Acad. Sci. USA 106, 2571–2576 (2009).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

E.A.D. and J.C. contributed equally to this Review. We thank C. Eichhorn and Q. Zhang for their input and assistance in the preparation of figures, and S. Butcher and S. Serganov for their comments on this Review. A.M.M. is supported by an NSF graduate research fellowship. The authors gratefully acknowledge the Michigan Economic Development Cooperation and the Michigan Technology Tri-Corridor for their support in the purchase of a 600 MHz spectrometer. This work was supported by the US National Institutes of Health (R01 AI066975 and R01 GM089846) and the US National Science Foundation (NSF Career Award CHE-0918817).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hashim M. Al-Hashimi.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Additional information

Reprints and permissions information is available at www.nature.com/reprints.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dethoff, E., Chugh, J., Mustoe, A. et al. Functional complexity and regulation through RNA dynamics. Nature 482, 322–330 (2012). https://doi.org/10.1038/nature10885

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature10885

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing