Please wait a minute...
Frontiers of Chemical Science and Engineering

ISSN 2095-0179

ISSN 2095-0187(Online)

CN 11-5981/TQ

Postal Subscription Code 80-969

2018 Impact Factor: 2.809

Front. Chem. Sci. Eng.    2016, Vol. 10 Issue (2) : 178-185    https://doi.org/10.1007/s11705-016-1558-2
REVIEW ARTICLE
Ribozyme and the mechanisms that underlie RNA catalysis
Timothy J. Wilson,Yijin Liu,David M. J. Lilley()
Cancer Research UK Nucleic Acid Structure Research Group, MSI/WTB Complex, The University of Dundee, Dundee DD1 5EH, UK
 Download: PDF(804 KB)   HTML
 Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks
Abstract

Ribozymes are widespread, and catalyze some extremely important reactions in the cell. Mechanistically most fall into one of two classes, using either metal ions or general acid-base catalysis. The nucleolytic ribozymes fall into the latter class, mostly using nucleobases. A sub-set of these use a combination of guanine base plus adenine acid to catalyze the cleavage reaction. New ribozymes are still being discovered at regular intervals and we can speculate on the potential existence of ribozymes that catalyze chemistry beyond phosphoryl transfer reactions, perhaps using small-molecule coenzymes.

Keywords RNA catalysis      RNA structure      catalytic mechanism     
Corresponding Author(s): David M. J. Lilley   
Online First Date: 18 February 2016    Issue Date: 19 May 2016
 Cite this article:   
Timothy J. Wilson,Yijin Liu,David M. J. Lilley. Ribozyme and the mechanisms that underlie RNA catalysis[J]. Front. Chem. Sci. Eng., 2016, 10(2): 178-185.
 URL:  
https://academic.hep.com.cn/fcse/EN/10.1007/s11705-016-1558-2
https://academic.hep.com.cn/fcse/EN/Y2016/V10/I2/178
Fig.1  Two alternative strategies for catalyzing phosphoryl transfer reactions. Both enzymes and ribozymes employ either metal ion catalysis or general acid-base catalysis for phosphoryl transfer reactions. Ribozymes such as the group I [19] and II introns [20] and RNase P use metal ion catalysis. The classical 2-metal ion model [21] is shown (A), although detailed chemical analysis of the group I intron ribozyme transition state indicates the presence of a third metal ion bound to the O2' of the attacking guanosine [2224]. In the general acid-base catalysis mechanism (B) a general base (denoted B) deprotonates the O2' nucleophile and a general acid (denoted A) donates a proton to the O5' leaving group
Fig.2  The active center of the VS ribozyme seen in the crystal structure of an G638A mutant [42]. This ribozyme uses nucleobase-mediated general acid-base catalysis. The general base is guanine 638, replaced by adenine in this mutant, and the general acid is adenine 756. G638 is poised to deprotonate the O2' nucleophile, and A756 is adjacent to the O5' leaving group
Fig.3  A comparison of the secondary structure of the hairpin and VS ribozymes drawn to highlight the equivalence of the two active sites [45]. The scissile phosphate (P circled) and the important adenine (red) and guanine (blue) nucleobases are highlighted for each ribozyme. The secondary structures are arranged to bring the interacting internal loops side by side, the A and B loops for the hairpin ribozyme and the substrate and A730 loops for the VS ribozyme. These regions are boxed in both ribozymes. These are drawn so that the strand polarities are the same for both ribozymes. It then becomes apparent that the key functionalities occupy the same positions with respect to the equivalent loops
Fig.4  The structure of the twister ribozyme. (A) The secondary structure of the ribozyme, with strongly conserved nucleotides highlighted red. The two tertiary interactions T1 (green) and T2 (purple) are indicated by broken lines. The position of ribozyme cleavage is indicated by the red arrow. In a majority of twister ribozymes there is an additional helix P3 at the position indicated. (B) The crystal structure of the ribozyme [39]. Cartoon representation of the RNA structure, with the tertiary interactions colored as in part (A)
Fig.5  A model of the active center of the twister ribozyme as the reaction approaches the transition state. This model was derived from the crystal structure by rotation of the base in the-1 position (green) to lie under G33. This brings the O2' nucleophile in-line. G33 is poised to remove the proton from the attacking O2' using N1. N2 of G33 stabilizes the transition state by hydrogen bonding to the proR non-bridging O of the scissile phosphate. A1 N3 is ready to donate a proton to the O5' leaving group; its pKa is raised by the interactions of N6 with successive phosphate groups within the T1 helix (colored pale green)
Fig.6  The structure of the TPP riboswitch from Arabidopsis thaliana bound to its thiamine pyrophosphate ligand [76]. (A) The overall structure of the riboswitch, with the bound TPP shown stick form in cyan. (B) Close view into the TPP binding cleft, with the riboswitch shown spacefilling. The thiazole ring of the TPP is clearly accessible from the solvent. The views were generated from PDB file 3D2G
1 Noller H F, Hoffarth V, Zimniak L. Unusual resistance of peptidyl transferase to protein extraction procedures. Science, 1992, 256: 1416–1419
2 Nissen P, Hansen J, Ba N, Moore P B, Steitz T A. The structural basis of ribosome activity in peptide bond synthesis. Science, 2000, 289: 920–930
3 Weinger J S, Parnell K M, Dorner S, Green R, Strobel S A. Substrate-assisted catalysis of peptide bond formation by the ribosome. Nature Structural & Molecular Biology, 2004, 11: 1101–1106
4 Kingery D A, Pfund E, Voorhees R M, Okuda K, Wohlgemuth I, Kitchen D E, Rodnina M V, Strobel S A. An uncharged amine in the transition state of the ribosomal peptidyl transfer reaction. Chemistry & Biology, 2008, 15: 493–500
5 Fica S M, Tuttle N, Novak T, Li N S, Lu J, Koodathingal P, Dai Q, Staley J P, Piccirilli J A. RNA catalyses nuclear pre-mRNA splicing. Nature, 2013, 503: 229–234
6 Keating K S, Toor N, Perlman P S, Pyle A M. A structural analysis of the group II intron active site and implications for the spliceosome. RNA (New York, N.Y.), 2010, 16: 1–9
7 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, 1983, 35: 849–857
8 Kikovska E, Svard S G, Kirsebom L A. Eukaryotic RNase P RNA mediates cleavage in the absence of protein. Proceedings of the National Academy of Sciences of the United States of America, 2007, 104: 2062–2067
9 Przybilski R, Graf S, Lescoute A, Nellen W, Westhof E, Steger G, Hammann C. Functional hammerhead ribozymes naturally encoded in the genome of Arabidopsis thaliana. Plant Cell, 2005, 17: 1877–1885
10 Seehafer C, Kalweit A, Steger G, Graf S, Hammann C. From alpaca to zebrafish: Hammerhead ribozymes wherever you look. RNA (New York, N.Y.), 2011, 17: 21–26
11 Salehi-Ashtiani K, Luptak A, Litovchick A, Szostak J W. A genomewide search for ribozymes reveals an HDV-like sequence in the human CPEB3 gene. Science, 2006, 313: 1788–1792
12 Webb C H, Riccitelli N J, Ruminski D J, Luptak A. Widespread occurrence of self-cleaving ribozymes. Science, 2009, 326: 953
13 Roth A, Weinberg Z, Chen A G, Kim P B, Ames T D, Breaker R R. A widespread self-cleaving ribozyme class is revealed by bioinformatics. Nature Chemical Biology, 2014, 10: 56–60
14 Weinberg Z, Kim P B, Chen T H, Li S, Harris K A, Lunse C E, Breaker R R. New classes of self-cleaving ribozymes revealed by comparative genomics analysis. Nature Chemical Biology, 2015, 11: 606–610
15 Lilley D M, Sutherland J. The chemical origins of life and its early evolution: An introduction. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 2011, 366: 2853–2856
16 Crick F H C. The origin of the genetic code. Journal of Molecular Biology, 1968, 38: 367–379
17 Orgel L E. RNA catalysis and the origin of life. Journal of Theoretical Biology, 1986, 123: 127–149
18 Wilson T J, Lilley D M J. The evolution of ribozyme chemistry. Science, 2009, 323: 1436–1438
19 Adams P L, Stahley M R, Wang J, Strobel S A. Crystal structure of a self-splicing group I intron with both exons. Nature, 2004, 430: 45–50
20 Marcia M, Pyle A M. Visualizing group II intron catalysis through the stages of splicing. Cell, 2012, 151: 497–507
21 Steitz T A, Steitz J A. A general 2-metal-ion mechanism for catalytic RNA. Proceedings of the National Academy of Sciences of the United States of America, 1993, 90: 6498–6502
22 Shan S, Kravchuk A V, Piccirilli J A, Herschlag D. Defining the catalytic metal ion interactions in the Tetrahymena ribozyme reaction. Biochemistry, 2001, 40: 5161–5171
23 Hougland J L, Kravchuk A V, Herschlag D, Piccirilli J A. Functional identification of catalytic metal ion binding sites within RNA. PLoS Biology, 2005, 3: e277
24 Frederiksen J K, Li N S, Das R, Herschlag D, Piccirilli J A. Metal-ion rescue revisited: Biochemical detection of site-bound metal ions important for RNA folding. RNA (New York, N.Y.), 2012, 18: 1123–1141
25 Golden B L, Gooding A R, Podell E, Cech T R. A preorganised active site in the crystal structure of the Tetrahymena ribozyme. Science, 1998, 282: 259–264
26 Stahley M R, Strobel S A. Structural evidence for a two-metal-ion mechanism of group I intron splicing. Science, 2005, 309: 1587–1590
27 Golden B L, Kim H D, Chase E. Crystal structure of a phage Twort group I ribozyme-product complex. Nature Structural & Molecular Biology, 2005, 12: 82–89
28 Toor N, Keating K S, Taylor S D, Pyle A M. Crystal structure of a self-spliced group II intron. Science, 2008, 320: 77–82
29 Gordon P M, Sontheimer E J, Piccirilli J A. Metal ion catalysis during the exon-ligation step of nuclear pre-mRNA splicing: Extending the parallels between the spliceosome and group II introns. RNA (New York, N.Y.), 2000, 6: 199–205
30 Huppler A, Nikstad L J, Allmann A M, Brow D A, Butcher S E. Metal binding and base ionization in the U6 RNA intramolecular stem-loop structure. Nature Structural Biology, 2002, 9: 431–435
31 Kazantsev A V, Krivenko A A, Pace N R. Mapping metal-binding sites in the catalytic domain of bacterial RNase P RNA. RNA (New York, N.Y.), 2009, 15: 266–276
32 Thompson J E, Raines R T. Value of general acid-base catalysis to Ribonuclease A. Journal of the American Chemical Society, 1994, 116: 5467–5468
33 Raines R T, Ribonuclease A. Chemical Reviews, 1998, 98: 1045–1066
34 Rupert P B, Ferré-D’Amaré A R. Crystal structure of a hairpin ribozyme-inhibitor complex with implications for catalysis. Nature, 2001, 410: 780–786
35 Ke A, Zhou K, Ding F, Cate J H, Doudna J A. A conformational switch controls hepatitis delta virus ribozyme catalysis. Nature, 2004, 429: 201–205
36 Martick M, Scott W G. Tertiary contacts distant from the active site prime a ribozyme for catalysis. Cell, 2006, 126: 309–320
37 Klein D J, Ferré-D’Amaré A R. Structural basis of glmS ribozyme activation by glucosamine-6-phosphate. Science, 2006, 313: 1752–1756
38 Cochrane J C, Lipchock S V, Strobel S A. Structural investigation of the GlmS ribozyme bound to its catalytic cofactor. Chemistry & Biology, 2007, 14: 97–105
39 Liu Y, Wilson T J, McPhee S A, Lilley D M. Crystal structure and mechanistic investigation of the twister ribozyme. Nature Chemical Biology, 2014, 10: 739–744
40 Eiler D, Wang J, Steitz T A. Structural basis for the fast self-cleavage reaction catalyzed by the twister ribozyme. Proceedings of the National Academy of Sciences of the United States of America, 2014, 111: 13028–13033
41 Ren A, Kosutic M, Rajashankar K R, Frener M, Santner T, Westhof E, Micura R, Patel D J. In-line alignment and Mg2+ coordination at the cleavage site of the env22 twister ribozyme. Nature Communications, 2014, 5: 5534
42 Suslov N B, DasGupta S, Huang H, Fuller J R, Lilley D M, Rice P A, Piccirilli J A. Crystal structure of the Varkud satellite ribozyme. Nature Chemical Biology, 2015, 11: 840–846
43 Han J, Burke J M. Model for general acid-base catalysis by the hammerhead ribozyme: pH-activity relationships of G8 and G12 variants at the putative active site. Biochemistry, 2005, 44: 7864–7870
44 Klein D J, Been M D, Ferré-D’Amaré A R. Essential role of an active-site guanine in glmS ribozyme catalysis. Journal of the American Chemical Society, 2007, 129: 14858–14859
45 Wilson T J, McLeod A C, Lilley D M J. A guanine nucleobase important for catalysis by the VS ribozyme. EMBO Journal, 2007, 26: 2489–2500
46 Cochrane J C, Lipchock S V, Smith K D, Strobel S A. Structural and chemical basis for glucosamine 6-phosphate binding and activation of the glmS ribozyme. Biochemistry, 2009, 48: 3239–3246
47 Kath-Schorr S, Wilson T J, Li N S, Lu J, Piccirilli J A, Lilley D M. General acid-base catalysis mediated by nucleobases in the hairpin ribozyme. Journal of the American Chemical Society, 2012, 134: 16717–16724
48 Lafontaine D A, Wilson T J, Norman D G, Lilley D M J. The A730 loop is an important component of the active site of the VS ribozyme. Journal of Molecular Biology, 2001, 312: 663–674
49 Rupert P B, Massey A P, Sigurdsson S T, Ferré-D'Amaré A R. Transition state stabilization by a catalytic RNA. Science, 2002, 298: 1421–1424
50 Wilson T J, Li N S, Lu J, Frederiksen J K, Piccirilli J A, Lilley D M J. Nucleobase-mediated general acid-base catalysis in the Varkud satellite ribozyme. Proceedings of the National Academy of Sciences of the United States of America, 2010, 107: 11751–11756
51 Wilson T J, Lilley D M J. Do the hairpin and VS ribozymes share a common catalytic mechanism based on general acid-base catalysis? A critical assessment of available experimental data. RNA (New York, N.Y.), 2011, 17: 213–221
52 Nakano S, Chadalavada D M, Bevilacqua P C. General acid-base catalysis in the mechanism of a hepatitis delta virus ribozyme. Science, 2000, 287: 1493–1497
53 Das S R, Piccirilli J A. General acid catalysis by the hepatitis delta virus ribozyme. Nature Chemical Biology, 2005, 1: 45–52
54 Chen J H, Yajima R, Chadalavada D M, Chase E, Bevilacqua P C, Golden B L A. 1.9 A crystal structure of the HDV ribozyme precleavage suggests both Lewis acid and general acid mechanisms contribute to phosphodiester cleavage. Biochemistry, 2010, 49: 6508–6518
55 McCarthy T J, Plog M A, Floy S A, Jansen J A, Soukup J K, Soukup G A. Ligand requirements for glmS ribozyme self-cleavage. Chemistry & Biology, 2005, 12: 1221–1226
56 Winkler W C, Nahvi A, Roth A, Collins J A, Breaker R R. Control of gene expression by a natural metabolite-responsive ribozyme. Nature, 2004, 428: 281–286
57 Prody G A, Bakos J T, Buzayan J M, Schneider I R, Bruening G. Autolytic processing of dimeric plant virus satellite RNA. Science, 1986, 231: 1577–1580
58 Forster A C, Symons R H. Self-cleavage of plus and minus RNAs of a virusoid and a structural model for the active sites. Cell, 1987, 49: 211–220
59 Lee T S, Silva L C, Giambasu G M, Martick M, Scott W G, York D M. Role of Mg2+ in hammerhead ribozyme catalysis from molecular simulation. Journal of the American Chemical Society, 2008, 130: 3053–3064
60 Thomas J M, Perrin D M. Probing general acid catalysis in the hammerhead ribozyme. Journal of the American Chemical Society, 2009, 131: 1135–1143
61 Johnston W K, Unrau P J, Lawrence M S, Glasner M E, Bartel D P. RNA-catalyzed RNA polymerization: Accurate and general RNA-templated primer extension. Science, 2001, 292: 1319–1325
62 Robertson M P, Joyce G F. Highly efficient self-replicating RNA enzymes. Chemistry & Biology, 2014, 21: 238–245
63 Attwater J, Wochner A, Holliger P. In-ice evolution of RNA polymerase ribozyme activity. Nature Chemistry, 2013, 5: 1011–1018
64 Ekland E H, Szostak J W, Bartel D P. Structurally complex and highly active RNA ligases derived from random RNA sequences. Science, 1995, 269: 364–370
65 Shechner D M, Grant R A, Bagby S C, Koldobskaya Y, Piccirilli J A, Bartel D P. Crystal structure of the catalytic core of an RNA-polymerase ribozyme. Science, 2009, 326: 1271–1275
66 Sengle G, Eisenfuhr A, Arora P S, Nowick J S, Famulok M. Novel RNA catalysts for the Michael reaction. Chemistry & Biology, 2001, 8: 459–473
67 Fusz S, Eisenfuhr A, Srivatsan S G, Heckel A, Famulok M. A ribozyme for the aldol reaction. Chemistry & Biology, 2005, 12: 941–950
68 Oberhuber M, Joyce G F. A DNA-templated aldol reaction as a model for the formation of pentose sugars in the RNA world. Angewandte Chemie, 2005, 44: 7580–7583
69 Seelig B, Jäschke A. A small catalytic RNA motif with Diels-Alderase activity. Chemistry & Biology, 1999, 6: 167–176
70 Benner S A, Ellington A D, Tauer A. Modern metabolism as a palimpsest of the RNA world. Proceedings of the National Academy of Sciences of the United States of America, 1989, 86: 7054–7058
71 Jadhav V R, Yarus M. Coenzymes as coribozymes. Biochimie, 2002, 84: 877–888
72 Breaker R R. Prospects for riboswitch discovery and analysis. Molecular Cell, 2011, 43: 867–879
73 Winkler W C, Breaker R R. Genetic control by metabolite-binding riboswitches. ChemBioChem, 2003, 4: 1024–1032
74 Winkler W, Nahvi A, Breaker R R. Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expression. Nature, 2002, 419: 952–956
75 Wang J, Daldrop P, Huang L, Lilley D M. The k-junction motif in RNA structure. Nucleic Acids Research, 2014, 42: 5322–5331
76 Thore S, Leibundgut M, Ban N. Structure of the eukaryotic thiamine pyrophosphate riboswitch with its regulatory ligand. Science, 2006, 312: 1208–1211
77 Serganov A, Polonskaia A, Phan A T, Breaker R R, Patel D J. Structural basis for gene regulation by a thiamine pyrophosphate-sensing riboswitch. Nature, 2006, 441: 1167–1171
[1] WANG Qian, YAO Zhong, XUN Zhijing, XU Xiaoying, XU Hong, WEI Ping. Properties and catalytic mechanism of -glutamyltranspeptidase from NX-2 [J]. Front. Chem. Sci. Eng., 2008, 2(4): 456-461.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed