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.

The chemical repertoire of natural ribozymes

Abstract

Although RNA is generally thought to be a passive genetic blueprint, some RNA molecules, called ribozymes, have intrinsic enzyme-like activity — they can catalyse chemical reactions in the complete absence of protein cofactors. In addition to the well-known small ribozymes that cleave phosphodiester bonds, we now know that RNA catalysts probably effect a number of key cellular reactions. This versatility has lent credence to the idea that RNA molecules may have been central to the early stages of life on Earth.

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: Mechanism of RNA-catalysed self-cleavage.
Figure 2: Structure of the hepatitis delta virus (HDV) ribozyme.
Figure 3: Structure of the hairpin ribozyme.
Figure 4: Self-splicing intron mechanisms.

Similar content being viewed by others

References

  1. Kruger, K. et al. Self-splicing RNA: autoexcision and autocyclization of the ribosomal RNA intervening sequence of Tetrahymena. Cell 31, 147–157 (1982).

    Article  CAS  PubMed  Google Scholar 

  2. Guerrier-Takada, C., Gardiner, K., Marsh, T., Pace, N. & Altman, S. The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme. Cell 35, 849–857 (1983).

    Article  CAS  PubMed  Google Scholar 

  3. Unrau, P. J. & Bartel, D. P. RNA-catalysed nucleotide synthesis. Nature 395, 260–263 (1998).

    Article  ADS  CAS  PubMed  Google Scholar 

  4. Lohse, P. A. & Szostak, J. W. Ribozyme-catalysed amino-acid transfer reactions. Nature 381, 442–444 (1996).

    Article  ADS  CAS  PubMed  Google Scholar 

  5. Wiegand, T. W., Janssen, R. C. & Eaton, B. E. Selection of RNA amide synthases. Chem. Biol. 4, 675–683 (1997).

    Article  CAS  PubMed  Google Scholar 

  6. Sengle, G., Eisenfuhr, A., Arora, P. S., Nowick, J. S. & Famulok, M. Novel RNA catalysts for the Michael reaction. Chem. Biol. 8, 459–473 (2001).

    Article  CAS  PubMed  Google Scholar 

  7. Jadhav, V. R. & Yarus, M. Acyl-CoAs from coenzyme ribozymes. Biochemistry 41, 723–729 (2002).

    Article  CAS  PubMed  Google Scholar 

  8. Wilson, D. S. & Szostak, J. W. In vitro selection of functional nucleic acids. Annu. Rev. Biochem. 68, 611–647 (1999).

    Article  CAS  PubMed  Google Scholar 

  9. Perrotta, A. T., Shih, I. & Been, M. D. Imidazole rescue of a cytosine mutation in a self-cleaving ribozyme. Science 286, 123–126 (1999).

    Article  CAS  PubMed  Google Scholar 

  10. Santoro, S. W., Joyce, G. F., Sakthivel, K., Gramatikova, S. & Barbas, C. F. III RNA cleavage by a DNA enzyme with extended chemical functionality. J. Am. Chem. Soc. 122, 2433–2439 (2000).

    Article  CAS  PubMed  Google Scholar 

  11. Tang, J. & Breaker, R. R. Rational design of allosteric ribozymes. Chem. Biol. 4, 453–459 (1997).

    Article  CAS  PubMed  Google Scholar 

  12. Salehi-Ashtiani, K. & Szostak, J. W. In vitro evolution suggests multiple origins for the hammerhead ribozyme. Nature 414, 82–84 (2001).

    Article  ADS  CAS  PubMed  Google Scholar 

  13. Murray, J. B., Seyhan, A. A., Walter, N. G., Burke, J. M. & Scott, W. G. The hammerhead, hairpin and VS ribozymes are catalytically proficient in monovalent cations alone. Chem. Biol. 5, 587–595 (1998).

    Article  CAS  PubMed  Google Scholar 

  14. 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 

  15. 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 

  16. Scott, W. G., Murray, J. B., Arnold, J. R., Stoddard, B. L. & Klug, A. Capturing the structure of a catalytic RNA intermediate: the hammerhead ribozyme. Science 274, 2065–2069 (1996).

    Article  ADS  CAS  PubMed  Google Scholar 

  17. Murray, J. B. et al. The structural basis of hammerhead ribozyme self-cleavage. Cell 92, 665–673 (1998).

    Article  CAS  PubMed  Google Scholar 

  18. Murray, J. B., Szoke, H., Szoke, A. & Scott, W. G. Capture and visualization of a catalytic RNA enzyme-product complex using crystal lattice trapping and X-ray holographic reconstruction. Mol. Cell 5, 279–287 (2000).

    Article  CAS  PubMed  Google Scholar 

  19. Murray, J. B., Dunham, C. M. & Scott, W. G. A pH-dependent conformational change, rather than the chemical step, appears to be rate-limiting in the hammerhead ribozyme cleavage reaction. J. Mol. Biol. 315, 121–130 (2002).

    Article  CAS  PubMed  Google Scholar 

  20. Scott, E. C. & Uhlenbeck, O. C. A re-investigation of the thio effect at the hammerhead cleavage site. Nucleic Acids Res. 27, 479–484 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Peracchi, A., Beigelman, L., Scott, E. C., Uhlenbeck, O. C. & Herschlag, D. Involvement of a specific metal ion in the transition of the hammerhead ribozyme to its catalytic conformation. J. Biol. Chem. 272, 26822–26826 (1997).

    Article  CAS  PubMed  Google Scholar 

  22. 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 

  23. Murray, J. B. & Scott, W. G. Does a single metal ion bridge the A-9 and scissile phosphate groups in the catalytically active hammerhead ribozyme structure? J. Mol. Biol. 296, 33–41 (2000).

    Article  CAS  PubMed  Google Scholar 

  24. O'Rear, J. L. et al. Comparison of the hammerhead cleavage reactions stimulated by monovalent and divalent cations. RNA 7, 537–545 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Curtis, E. A. & Bartel, D. P. The hammerhead cleavage reaction in monovalent cations. RNA 7, 546–552 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. 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 

  27. Rupert, P. B. & Ferre-D'Amare, A. R. Crystal structure of a hairpin ribozyme-inhibitor complex with implications for catalysis. Nature 410, 780–786 (2001).

    Article  ADS  CAS  PubMed  Google Scholar 

  28. Rajagopal, P. & Feigon, J. Triple-strand formation in the homopurine:homopyrimidine DNA oligonucleotides d(G-A)4 and d(T-C)4. Nature 339, 637–640 (1989).

    Article  ADS  CAS  PubMed  Google Scholar 

  29. Sklenar, V. & Feigon, J. Formation of a stable triplex from a single DNA strand. Nature 345, 836–838 (1990).

    Article  ADS  CAS  PubMed  Google Scholar 

  30. Connell, G. J. & Yarus, M. RNAs with dual specificity and dual RNAs with similar specificity. Science 264, 1137–1141 (1994).

    Article  ADS  CAS  PubMed  Google Scholar 

  31. Legault, P. & Pardi, A. In situ probing of adenine protonation in RNA by 13C NMR. J. Am. Chem. Soc. 116, 8390–8391 (1994).

    Article  CAS  Google Scholar 

  32. Ravindranathan, S., Butcher, S. E. & Feigon, J. Adenine protonation in domain B of the hairpin ribozyme. Biochemistry 39, 16026–16032 (2000).

    Article  CAS  PubMed  Google Scholar 

  33. Shih, I. H. & Been, M. D. Involvement of a cytosine side chain in proton transfer in the rate-determining step of ribozyme self-cleavage. Proc. Natl Acad. Sci. USA 98, 1489–1494 (2001).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  34. Nakano, S., Chadalavada, D. M. & Bevilacqua, P. C. General acid-base catalysis in the mechanism of a hepatitis delta virus ribozyme. Science 287, 1493–1497 (2000).

    Article  ADS  CAS  PubMed  Google Scholar 

  35. Nakano, S. & Bevilacqua, P. C. Proton inventory of the genomic HDV ribozyme in Mg2+-containing solutions. J. Am. Chem. Soc. 123, 11333–11334 (2001).

    Article  CAS  PubMed  Google Scholar 

  36. Luptak, A., Ferre-D'Amare, A. R., Zhou, K., Zilm, K. W. & Doudna, J. A. Direct pKa measurement of the active-site cytosine in a genomic hepatitis delta virus ribozyme. J. Am. Chem. Soc. 123, 8447–8452 (2001).

    Article  CAS  PubMed  Google Scholar 

  37. Nakano, S., Proctor, D. J. & Bevilacqua, P. C. Mechanistic characterization of the HDV genomic ribozyme: assessing the catalytic and structural contributions of divalent metal ions within a multichannel reaction mechanism. Biochemistry 40, 12022–12038 (2001).

    Article  CAS  PubMed  Google Scholar 

  38. Ryder, S. P. et al. Investigation of adenosine base ionization in the hairpin ribozyme by nucleotide analog interference mapping. RNA 7, 1454–1463 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Hampel, A. & Cowan, J. A. A unique mechanism for RNA catalysis: the role of metal cofactors in hairpin ribozyme cleavage. Chem. Biol. 4, 513–517 (1997).

    Article  CAS  PubMed  Google Scholar 

  40. Nesbitt, S., Hegg, L. A. & Fedor, M. J. An unusual pH-independent and metal-ion-independent mechanism for hairpin ribozyme catalysis. Chem. Biol. 4, 619–630 (1997).

    Article  CAS  PubMed  Google Scholar 

  41. Walter, N. G. & Burke, J. M. The hairpin ribozyme: structure, assembly and catalysis. Curr. Opin. Chem. Biol. 2, 303 (1998).

    Article  CAS  PubMed  Google Scholar 

  42. Cech, T. R. & Herschlag, D. (eds) Group I Ribozymes: Substrate Recognition, Catalytic Strategies and Comparative Mechanistic Analysis (Springer, Berlin, 1996).

    Google Scholar 

  43. Narlikar, G. J. & Herschlag, D. Mechanistic aspects of enzymatic catalysis: lessons from comparison of RNA and protein enzymes. Annu. Rev. Biochem. 66, 19–59 (1997).

    Article  CAS  PubMed  Google Scholar 

  44. Shan, S., Kravchuk, A. V., Piccirilli, J. A. & Herschlag, D. Defining the catalytic metal ion interactions in the Tetrahymena ribozyme reaction. Biochemistry 40, 5161–5171 (2001).

    Article  CAS  PubMed  Google Scholar 

  45. Cate, J. H. et al. Crystal structure of a group I ribozyme domain: principles of RNA packing. Science 273, 1678–1685 (1996).

    Article  ADS  CAS  PubMed  Google Scholar 

  46. Juneau, K., Podell, E., Harrington, D. J. & Cech, T. R. Structural basis of the enhanced stability of a mutant ribozyme domain and a detailed view of RNA–solvent interactions. Structure (Camb.) 9, 221–231 (2001).

    Article  CAS  Google Scholar 

  47. Golden, B. L., Gooding, A. R., Podell, E. R. & Cech, T. R. A preorganized active site in the crystal structure of the Tetrahymena ribozyme. Science 282, 259–264 (1998).

    Article  ADS  CAS  PubMed  Google Scholar 

  48. Michel, F. & Westhof, E. Modelling of the three-dimensional architecture of group I catalytic introns based on comparative sequence analysis. J. Mol. Biol. 216, 585–610 (1990).

    Article  CAS  PubMed  Google Scholar 

  49. Szewczak, A. A. et al. An important base triple anchors the substrate helix recognition surface within the Tetrahymena ribozyme active site. Proc. Natl Acad. Sci. USA 96, 11183–11188 (1999).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  50. Gordon, P. M., Sontheimer, E. J. & Piccirilli, J. A. Kinetic characterization of the second step of group II intron splicing: role of metal ions and the cleavage site 2′-OH in catalysis. Biochemistry 39, 12939–12952 (2000).

    Article  CAS  PubMed  Google Scholar 

  51. Sigel, R. K., Vaidya, A. & Pyle, A. M. Metal ion binding sites in a group II intron core. Nature Struct. Biol. 7, 1111–1116 (2000).

    Article  CAS  PubMed  Google Scholar 

  52. Gordon, P. M. & Piccirilli, J. A. Metal ion coordination by the AGC triad in domain 5 contributes to group II intron catalysis. Nature Struct. Biol. 8, 893–898 (2001).

    Article  CAS  PubMed  Google Scholar 

  53. Jestin, J. L., Deme, E. & Jacquier, A. Identification of structural elements critical for inter-domain interactions in a group II self-splicing intron. EMBO J. 16, 2945–2954 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Boudvillain, M., de Lencastre, A. & Pyle, A. M. A tertiary interaction that links active-site domains to the 5′ splice site of a group II intron. Nature 406, 315–318 (2000).

    Article  ADS  CAS  PubMed  Google Scholar 

  55. Chu, V. T., Adamidi, C., Liu, Q., Perlman, P. S. & Pyle, A. M. Control of branch-site choice by a group II intron. EMBO J. 20, 6866–6876 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Zhang, L. & Doudna, J. A. Structural insights into group II intron catalysis and branch-site selection. Science 295, 2084–2088 (2002).

    Article  ADS  CAS  PubMed  Google Scholar 

  57. Costa, M., Michel, F. & Westhof, E. A three-dimensional perspective on exon binding by a group II self-splicing intron. EMBO J. 19, 5007–5018 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Swisher, J., Duarte, C. M., Su, L. J. & Pyle, A. M. Visualizing the solvent-inaccessible core of a group II intron ribozyme. EMBO J. 20, 2051–2061 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Yang, J., Zimmerly, S., Perlman, P. S. & Lambowitz, A. M. Efficient integration of an intron RNA into double-stranded DNA by reverse splicing. Nature 381, 332–335 (1996).

    Article  ADS  CAS  PubMed  Google Scholar 

  60. Frank, D. N. & Pace, N. R. Ribonuclease P: unity and diversity in a tRNA processing ribozyme. Annu. Rev. Biochem. 67, 153–180 (1998).

    Article  CAS  PubMed  Google Scholar 

  61. Morl, M. & Marchfelder, A. The final cut. The importance of tRNA 3′-processing. EMBO Rep. 2, 17–20 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Warnecke, J. M., Held, R., Busch, S. & Hartmann, R. K. Role of metal ions in the hydrolysis reaction catalyzed by RNase P RNA from Bacillus subtilis. J. Mol. Biol. 290, 433–445 (1999).

    Article  CAS  PubMed  Google Scholar 

  63. Warnecke, J. M., Sontheimer, E. J., Piccirilli, J. A. & Hartmann, R. K. Active site constraints in the hydrolysis reaction catalyzed by bacterial RNase P: analysis of precursor tRNAs with a single 3′-S-phosphorothiolate internucleotide linkage. Nucleic Acids Res. 28, 720–727 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Westhof, E. & Altman, S. Three-dimensional working model of M1 RNA, the catalytic RNA subunit of ribonuclease P from Escherichia coli. Proc. Natl Acad. Sci. USA 91, 5133–5137 (1994).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  65. Harris, M. E., Kazantsev, A. V., Chen, J. L. & Pace, N. R. Analysis of the tertiary structure of the ribonuclease P ribozyme-substrate complex by site-specific photoaffinity crosslinking. RNA 3, 561–576 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Frank, D. N., Adamidi, C., Ehringer, M. A., Pitulle, C. & Pace, N. R. Phylogenetic-comparative analysis of the eukaryal ribonuclease P RNA. RNA 6, 1895–1904 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Li, Y. & Altman, S. A subunit of human nuclear RNase P has ATPase activity. Proc. Natl Acad. Sci. USA 98, 441–444 (2001).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  68. Xiao, S., Houser-Scott, F. & Engelke, D. R. Eukaryotic ribonuclease P: increased complexity to cope with the nuclear pre-tRNA pathway. J. Cell. Physiol. 187, 11–20 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Tesmer, J. J. et al. Two-metal-ion catalysis in adenylyl cyclase. Science 285, 756–760 (1999).

    Article  CAS  PubMed  Google Scholar 

  70. Wyckoff, H. W. et al. The three-dimensional structure of ribonuclease-S. Interpretation of an electron density map at a nominal resolution of 2 Å. J. Biol. Chem. 245, 305–328 (1970).

    CAS  PubMed  Google Scholar 

  71. Drum, C. L. et al. Structural basis for the activation of anthrax adenylyl cyclase exotoxin by calmodulin. Nature 415, 396–402 (2002).

    Article  ADS  CAS  PubMed  Google Scholar 

  72. Treiber, D. K. & Williamson, J. R. Exposing the kinetic traps in RNA folding. Curr. Opin. Struct. Biol. 9, 339–345 (1999).

    Article  CAS  PubMed  Google Scholar 

  73. Thirumalai, D. & Woodson, S. A. Maximizing RNA folding rates: a balancing act. RNA 6, 790–794 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Thirumalai, D., Lee, N., Woodson, S. A. & Klimov, D. Early events in RNA folding. Annu. Rev. Phys. Chem. 52, 751–762 (2001).

    Article  ADS  CAS  PubMed  Google Scholar 

  75. 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 

  76. Zhuang, X. et al. A single-molecule study of RNA catalysis and folding. Science 288, 2048–2051 (2000).

    Article  ADS  CAS  PubMed  Google Scholar 

  77. Liphardt, J., Onoa, B., Smith, S. B., Tinoco, I. J. & Bustamante, C. Reversible unfolding of single RNA molecules by mechanical force. Science 292, 733–737 (2001).

    Article  ADS  CAS  PubMed  Google Scholar 

  78. Russell, R. et al. Exploring the folding landscape of a structured RNA. Proc. Natl Acad. Sci. USA 99, 155–160 (2002).

    Article  ADS  CAS  PubMed  Google Scholar 

  79. Caprara, M. G., Mohr, G. & Lambowitz, A. M. A tyrosyl-tRNA synthetase protein induces tertiary folding of the group I intron catalytic core. J. Mol. Biol. 257, 512–531 (1996).

    Article  CAS  PubMed  Google Scholar 

  80. Weeks, K. M. & Cech, T. R. Assembly of a ribonucleoprotein catalyst by tertiary structure capture. Science 271, 345–348 (1996).

    Article  ADS  CAS  PubMed  Google Scholar 

  81. Chanfreau, G. & Jacquier, A. An RNA conformational change between the two chemical steps of group II self-splicing. EMBO J. 15, 3466–3476 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Cohen, S. B. & Cech, T. R. Dynamics of thermal motions within a large catalytic RNA investigated by cross-linking with thiol-disulfide interchange. J. Am. Chem. Soc. 119, 6259–6268 (1997).

    Article  CAS  Google Scholar 

  83. Profenno, L. A., Kierzek, R., Testa, S. M. & Turner, D. H. Guanosine binds to the Tetrahymena ribozyme in more than one step, and its 2′-OH and the nonbridging pro-Sp phosphoryl oxygen at the cleavage site are required for productive docking. Biochemistry 36, 12477–12485 (1997).

    Article  CAS  PubMed  Google Scholar 

  84. Murchie, A. I., Thomson, J. B., Walter, F. & Lilley, D. M. Folding of the hairpin ribozyme in its natural conformation achieves close physical proximity of the loops. Mol. Cell 1, 873–881 (1998).

    Article  CAS  PubMed  Google Scholar 

  85. Andersen, A. A. & Collins, R. A. Rearrangement of a stable RNA secondary structure during VS ribozyme catalysis. Mol. Cell 5, 469–478 (2000).

    Article  CAS  PubMed  Google Scholar 

  86. Noller, H. F., Hoffarth, V. & Zimniak, L. Unusual resistance of peptidyl transferase to protein extraction procedures. Science 256, 1416–1419 (1992).

    Article  ADS  CAS  PubMed  Google Scholar 

  87. Ban, N., Nissen, P., Hansen, J., Moore, P. B. & Steitz, T. A. The complete atomic structure of the large ribosomal subunit at 2.4 Å resolution. Science 289, 905–920 (2000).

    Article  ADS  CAS  PubMed  Google Scholar 

  88. Welch, M., Chastang, J. & Yarus, M. An inhibitor of ribosomal peptidyl transferase using transition-state analogy. Biochemistry 34, 385–390 (1995).

    Article  CAS  PubMed  Google Scholar 

  89. Nissen, P., Hansen, J., Ban, N., Moore, P. B. & Steitz, T. A. The structural basis of ribosome activity in peptide bond synthesis. Science 289, 920–930 (2000).

    Article  ADS  CAS  PubMed  Google Scholar 

  90. Polacek, N., Gaynor, M., Yassin, A. & Mankin, A. S. Ribosomal peptidyl transferase can withstand mutations at the putative catalytic nucleotide. Nature 411, 498–501 (2001).

    Article  ADS  CAS  PubMed  Google Scholar 

  91. Thompson, J. et al. Analysis of mutations at residues A2451 and G2447 of 23S rRNA in the peptidyltransferase active site of the 50S ribosomal subunit. Proc. Natl Acad. Sci. USA 98, 9002–9007 (2001).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  92. Murray, J. M. & Doudna, J. A. Creative catalysis: pieces of the RNA world jigsaw. Trends Biochem. Sci. 26, 699–701 (2001).

    Article  CAS  PubMed  Google Scholar 

  93. Kumar, R. K. & Yarus, M. RNA-catalyzed amino acid activation. Biochemistry 40, 6998–7004 (2001).

    Article  CAS  PubMed  Google Scholar 

  94. Illangasekare, M. & Yarus, M. Specific, rapid synthesis of Phe-RNA by RNA. Proc. Natl Acad. Sci. USA 96, 5470–5475 (1999).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  95. Illangasekare, M. & Yarus, M. A tiny RNA that catalyzes both aminoacyl-RNA and peptidyl-RNA synthesis. RNA 5, 1482–1489 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Collins, C. A. & Guthrie, C. The question remains: is the spliceosome a ribozyme? Nature Struct. Biol. 7, 850–854 (2000).

    Article  CAS  PubMed  Google Scholar 

  97. Yean, S. L., Wuenschell, G., Termini, J. & Lin, R. J. Metal-ion coordination by U6 small nuclear RNA contributes to catalysis in the spliceosome. Nature 408, 881–884 (2000).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  98. Valadkhan, S. & Manley, J. L. Splicing-related catalysis by protein-free snRNAs. Nature 413, 701–707 (2001).

    Article  ADS  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We acknowledge D. Battle for extensive help with figure preparation, and V. Rath for comments on the manuscript.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Doudna, J., Cech, T. The chemical repertoire of natural ribozymes. Nature 418, 222–228 (2002). https://doi.org/10.1038/418222a

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/418222a

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