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Ribozyme speed limits
Open accessAbstract
The speed at which RNA molecules decompose is a critical determinant of many biological processes, including those directly involved in the storage and expression of genetic information. One mechanism for RNA cleavage involves internal phosphoester transfer, wherein the 2′-oxygen atom carries out an S N 2-like nucleophilic attack on the adjacent phosphorus center (transesterification). In this article, we discuss fundamental principles of RNA transesterification and define a conceptual framework that can be used to assess the catalytic power of enzymes that cleave RNA. We deduce that certain ribozymes and deoxyribozymes, like their protein enzyme counterparts, can bring about enormous rate enhancements.
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“All of these tasks might be performed by RNA (Narlikar and Herschlag 1997;Emilsson et al. 2003), acting either alone (Strobel and Ortoleva-Donnelly 1999) or with the help of a suitably positioned metal cation or other cofactor (Shan et al. 1999(Shan et al. , 2001)).”
From Protocells and RNA Self-Replication (2018) · cites this paper as Emilsson et al. 2003
Citations
Cites
Catalysis in chemistry and enzymology
Jencks, W. P. (1969) · Medical Entomology and Zoology · Cited by 3,217
Structure and Mechanism in Protein Science
Fersht, A. (2017) · WORLD SCIENTIFIC eBooks · doi:10.1142/10574 · Cited by 2,053
Westheimer, F. H. (1987) · Science · doi:10.1126/science.2434996 · Cited by 1,711 · cited 2×
“Both the stability of phosphate esters and their chemical pliability have been suggested as foremost reasons why a phosphate ester has emerged as the backbone of choice for the molecules responsible for genetic information storage and transfer (Westheimer 1987).”
BackgroundA general purpose RNA-cleaving DNA enzyme
Santoro, S. W., & Joyce, G. F. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.9.4262 · Cited by 1,546
In Vitro Selection of Functional Nucleic Acids
Wilson, D. S., & Szostak, J. W. (1999) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.68.1.611 · Cited by 1,217
A general two-metal-ion mechanism for catalytic RNA
Steitz, T. A., & Steitz, J. A. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.14.6498 · Cited by 1,171
Raines, R. T. (1998) · Chemical Reviews · doi:10.1021/cr960427h · Cited by 938
Pseudo-rotation in the hydrolysis of phosphate esters
Westheimer, F. H. (1968) · Accounts of Chemical Research · doi:10.1021/ar50003a002 · Cited by 772
Li, Y., & Breaker, R. R. (1999) · Journal of the American Chemical Society · doi:10.1021/ja990592p · Cited by 587
Self-citationRelationship between internucleotide linkage geometry and the stability of RNA
Soukup, G. A., & Breaker, R. R. (1999) · RNA · doi:10.1017/s1355838299990891 · Cited by 549
Self-citationEnzyme Mechanisms, Models, and Mimics
Kirby, A. J. (1996) · Angewandte Chemie International Edition in English · doi:10.1002/anie.199607061 · Cited by 526
24 Bovine Pancreatic Ribonuclease
Richards, F. M., & Wyckoff, H. W. (1971) · The Enzymes · doi:10.1016/s1874-6047(08)60384-4 · Cited by 441
Oivanen, M., Kuusela, S., & Lönnberg, H. (1998) · Chemical Reviews · doi:10.1021/cr960425x · Cited by 438
General Acid-Base Catalysis in the Mechanism of a Hepatitis Delta Virus Ribozyme
Nakano, S., Chadalavada, D. M., & Bevilacqua, P. C. (2000) · Science · doi:10.1126/science.287.5457.1493 · Cited by 384
Chemical Basis for Enzyme Catalysis
Bruice, T. C., & Benkovic, S. J. (2000) · Biochemistry · doi:10.1021/bi0003689 · Cited by 303
Trawick, B. N., Daniher, A. T., & Bashkin, J. K. (1998) · Chemical Reviews · doi:10.1021/cr960422k · Cited by 280
Mechanism and Catalysis of Nucleophilic Substitution in Phosphate Esters
Thatcher, R. J., & Kluger, R. (1989) · Advances in physical organic chemistry · doi:10.1016/s0065-3160(08)60019-2 · Cited by 277
Unifying the Current Data on the Mechanism of Cleavage–Transesterification of RNA
Perreault, D. M., & Anslyn, E. V. (1997) · Angewandte Chemie International Edition in English · doi:10.1002/anie.199704321 · Cited by 277
Structure and function of the hairpin ribozyme
Fedor, M. J. (2000) · Journal of Molecular Biology · doi:10.1006/jmbi.2000.3560 · Cited by 248
In Vitro Selection of Catalytic Polynucleotides
Breaker, R. R. (1997) · Chemical Reviews · doi:10.1021/cr960008k · Cited by 240
Self-citationMapping the transition state for ATP hydrolysis: implications for enzymatic catalysis
Admiraal, S. J., & Herschlag, D. (1995) · Chemistry & Biology · doi:10.1016/1074-5521(95)90101-9 · Cited by 204
Zhou, D., & Taira, K. (1998) · Chemical Reviews · doi:10.1021/cr9604292 · Cited by 195
Stage-Zimmermann, T. K., & Uhlenbeck, O. C. (1998) · RNA · doi:10.1017/s1355838298980876 · Cited by 194
Järvinen, P., Oivanen, M., & Lönnberg, H. (1991) · The Journal of Organic Chemistry · doi:10.1021/jo00018a037 · Cited by 184
Solution Structure of Loop A from the Hairpin Ribozyme from Tobacco Ringspot Virus Satellite
Cai, Z., & Tinoco, I. (1996) · Biochemistry · doi:10.1021/bi952985g · Cited by 174
Unusual Dynamics and pKaShift at the Active Site of a Lead-Dependent Ribozyme
Legault, P., & Pardi, A. (1997) · Journal of the American Chemical Society · doi:10.1021/ja9640051 · Cited by 170
Breslow, R. (1991) · Accounts of Chemical Research · doi:10.1021/ar00011a001 · Cited by 158
A common speed limit for RNA-cleaving ribozymes and deoxyribozymes
Breaker, R. R., Emilsson, G. M., Lazarev, D. S., Nakamura, S., Puskarz, I., Roth, A., & Sudarsan, N. (2003) · RNA · doi:10.1261/rna.5670703 · Cited by 151
Self-citationBrown, D. M., & Todd, A. R. (1952) · Journal of the Chemical Society (Resumed) · doi:10.1039/jr9520000052 · Cited by 147
Guthrie, J. P. (1977) · Journal of the American Chemical Society · doi:10.1021/ja00454a018 · Cited by 134
The hairpin ribozyme: structure, assembly and catalysis
Walter, N. G., & Burker, J. M. (1998) · Current Opinion in Chemical Biology · doi:10.1016/s1367-5931(98)80032-x · Cited by 121
Izatt, R. M., Rytting, J. H., Hansen, L. D., & Christensen, J. J. (1966) · Journal of the American Chemical Society · doi:10.1021/ja00964a003 · Cited by 121
Structural diversity of self-cleaving ribozymes
Tang, J. Y., & Breaker, R. R. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.11.5784 · Cited by 112
Self-citationThe pKa's of 2‘-Hydroxyl Group in Nucleosides and Nucleotides
Velikyan, I., Acharya, S., Trifonova, A., Földesi, A., & CHATTOPADHYAYA, J. B. (2001) · Journal of the American Chemical Society · doi:10.1021/ja0036312 · Cited by 107
Direct pKa Measurement of the Active-Site Cytosine in a Genomic Hepatitis Delta Virus Ribozyme
Lupták, A., Ferré-D’Amaré, A. R., Zhou, K., Zilm, K. W., & Doudna, J. A. (2001) · Journal of the American Chemical Society · doi:10.1021/ja016091x · Cited by 105
Wedekind, J. E., & McKay, D. (1998) · Annual Review of Biophysics and Biomolecular Structure · doi:10.1146/annurev.biophys.27.1.475 · Cited by 103
Structure, folding and activity of the VS ribozyme: importance of the 2‐3‐6 helical junction
Lafontaine, D. A., Norman, D., & Lilley, D. M. J. (2001) · The EMBO Journal · doi:10.1093/emboj/20.6.1415 · Cited by 95
Bruice, T. C., Tsubouchi, A., Dempcy, R. O., & Olson, L. P. (1996) · Journal of the American Chemical Society · doi:10.1021/ja9607300 · Cited by 89
6 Chemical Basis of Biological Phosphoryl Transfer
Benkovic, S. J., & Schray, K. J. (1973) · The Enzymes · doi:10.1016/s1874-6047(08)60066-9 · Cited by 86
Limits to Catalysis by Ribonuclease A
Thompson, J. E., Kutateladze, T. G., Schuster, M. C., Venegas, F. D., Messmore, J. M., & Raines, R. T. (1995) · Bioorganic Chemistry · doi:10.1006/bioo.1995.1033 · Cited by 83
A re-investigation of the thio effect at the hammerhead cleavage site
Scott, E. C., & Uhlenbeck, O. C. (1999) · Nucleic Acids Research · doi:10.1093/nar/27.2.479 · Cited by 82
Structure and mechanism in protein science a guide to enzyme catalysis and protein folding
Fersht, A. (2000) · Cited by 80
Hydrolysis of Esters of Monoribonucleotides
Brown, D. M., Magrath, D. I., NEILSON, A. H., & Todd, A. R. (1956) · Nature · doi:10.1038/1771124a0 · Cited by 70
416. Nucleotides. Part XXI. The action of ribonuclease on simple esters of the monoribonucleotides
Brown, D. M., & Todd, A. R. (1953) · Journal of the Chemical Society (Resumed) · doi:10.1039/jr9530002040 · Cited by 67
The Mechanism of the Alkaline Hydrolysis of Ribonucleic Acids
Lipkin, D., Talbert, P. T., & Cohn, M. (1954) · Journal of the American Chemical Society · doi:10.1021/ja01640a004 · Cited by 65
Oivanen, M., Ora, M., Almer, H., Strömberg, R., & Lönnberg, H. (1995) · The Journal of Organic Chemistry · doi:10.1021/jo00122a050 · Cited by 62
Lim, C., & Karplus, M. (1990) · Journal of the American Chemical Society · doi:10.1021/ja00171a033 · Cited by 58
Examination of the catalytic fitness of the hammerhead ribozyme by in vitro selection.
Tang, J. Y., & Breaker, R. R. (1997) · PubMed · Cited by 58
Self-citationZhou, D., Usman, N., Wincott, F. E., Matulić‐Adamić, J., Orita, M., Zhang, L., Komiyama, M., Kumar, P. K. R., & Taira, K. (1996) · Journal of the American Chemical Society · doi:10.1021/ja9606790 · Cited by 56
Synthesis and Properties of Diuridine Phosphate Analogues Containing Thio and Amino Modifications
Thomson, J. B., Patel, B. K., Jimenez, V. M., Jr., Eckart, K., & Eckstein, F. (1996) · The Journal of Organic Chemistry · doi:10.1021/jo960795l · Cited by 52
Biophysical and biochemical investigations of RNA catalysis in the hammerhead ribozyme
Scott, W. G. (1999) · Quarterly Reviews of Biophysics · doi:10.1017/s003358350000353x · Cited by 51
Selection of novel Mg(2+)‐dependent self‐cleaving ribozymes.
Williams, K. P., Ciafrè, S., & Tocchini‐Valentini, G. P. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb00134.x · Cited by 48
Kuimelis, R. G., & McLaughlin, L. W. (1995) · Nucleic Acids Research · doi:10.1093/nar/23.23.4753 · Cited by 46
Sood, V. D., & Collins, R. A. (2002) · Journal of Molecular Biology · doi:10.1016/s0022-2836(02)00521-1 · Cited by 42
Structure and function of the small ribozymes
Butcher, S. E. (2001) · Current Opinion in Structural Biology · doi:10.1016/s0959-440x(00)00207-4 · Cited by 37
Ribozyme activity in the genomic and antigenomic RNA strands of hepatitis delta virus
Wadkins, T. S., & Been, M. D. (2002) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-002-8409-7 · Cited by 34
Roberts, R., & Halford, S. E. (1993) · Cited by 32
The Kinetics of Hydrolysis of Ribonucleic Acid
Bacher, J. E., & Kauzmann, W. (1952) · Journal of the American Chemical Society · doi:10.1021/ja01135a020 · Cited by 30
1 Mechanistic Principles of Enzyme-catalyzed Cleavage of Phosphodiester BondsPreprint
Gerlt, J. A. (1993) · Cold Spring Harbor Monograph Archive · doi:10.1101/087969426.25.1 · Cited by 29
Kosonen, M., & Lönnberg, H. (1995) · Journal of the Chemical Society Perkin Transactions 2 · doi:10.1039/p29950001203 · Cited by 28
Almer, H., & Strömberg, R. (1996) · Journal of the American Chemical Society · doi:10.1021/ja953399d · Cited by 27
Physical Properties of Nucleotides: Charge Densities, pK Values, Spectra, and Tautomerism
Saenger, W. (1984) · Springer advanced texts in chemistry · doi:10.1007/978-1-4612-5190-3_5 · Cited by 27
Hammerhead Cleavage of the Phosphorodithioate Linkage
Derrick, W. B., Greef, C. H., Caruthers, M. H., & Uhlenbeck, O. C. (2000) · Biochemistry · doi:10.1021/bi000146a · Cited by 22
Thermodynamics of proton dissociation in dilute aqueous solution
Christensen, J., SMITH, D. E., Slade, M. D., & Izatt, R. M. (1972) · Thermochimica Acta · doi:10.1016/0040-6031(72)80016-9 · Cited by 21
Substrate specificity and reaction kinetics of an X-motif ribozyme
Lazarev, D. S., Puskarz, I., & Breaker, R. R. (2003) · RNA · doi:10.1261/rna.2600503 · Cited by 19
Self-citationPhenyl ester of adenosine 3′-Phosphate as a novel probe for the rate-limiting step in RNA hydrolysis
Shiiba, T., & Komiyama, M. (1992) · Tetrahedron Letters · doi:10.1016/s0040-4039(00)61148-6 · Cited by 12
Degradation and modification of nucleic acids
ADAMS, R. L. P., Knowler, J. T., & Leader, D. P. (1986) · Springer eBooks · doi:10.1007/978-94-009-4103-8_4 · Cited by 8
Organization and Expression of the Hepatitis Delta Virus Genome
Taylor, J. M. (1997) · Seminars in Virology · doi:10.1006/smvy.1997.0106 · Cited by 4
Degradation and modification of nucleic acids
ADAMS, R. L. P., Knowler, J. T., & Leader, D. P. (1992) · Springer eBooks · doi:10.1007/978-94-011-2290-0_4 · Cited by 3
Shiiba, T., & Komiyama, M. (1992) · PubMed · Cited by 1
Research works printed but not linked: 5
- Carlson, W.D. 1976. “X-ray diffraction studies of bovine pancreatic ribonuclease-S and E. coli alkaline phosphatase.” Ph.D. thesis, Yale University, New Haven, CT.
- 1996, Angew. Chem. Int. Ed. Engl., 35, 707
- 1995, J. Chem. Soc. Perkin Trans., 2, 1203
- March, J. 1992. Acids and bases. In Advanced organic chemistry, 4th ed., pp. 248–272. John Wiley & Sons, New York.
- 1997, RNA, 3, 914
Cited by
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Winkler, W. C., Nahvi, A., Roth, A., Collins, J. A., & Breaker, R. R. (2004) · Nature · doi:10.1038/nature02362 · Cited by 976
Self-citationChemistry, structure and function of approved oligonucleotide therapeutics
Egli, M., & Manoharan, M. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad067 · Cited by 909
RNA Structural Dynamics As Captured by Molecular Simulations: A Comprehensive Overview
Šponer, J., Bussi, G., Krepl, M., Banáš, P., Bottaro, S., Cunha, R. A., Gil-Ley, A., Pinamonti, G., Poblete, S., Jurečka, P., et al. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00427 · Cited by 606
Robertson, M. P., & Joyce, G. F. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a003608 · Cited by 556
McConnell, E. M., Cozma, I., Mou, Q., Brennan, J. D., Lu, Y., & Li, Y. (2021) · Chemical Society Reviews · doi:10.1039/d1cs00240f · Cited by 492
Metadata
- Authors
- EMILSSON, G. M., NAKAMURA, S., ROTH, A., & BREAKER, R. R.
- Affiliations
- Yale University (US)
- Corresponding author
- BREAKER, RONALD R.
- Venue
- RNA
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2003-07-17
- Volume
- 9
- Issue
- 8
- Pages
- 907-918
- ISSN
- 1355-8382 (ISSN-L)
- 1469-9001
- PMC
- PMC1370456
- OpenAlex
- W2160498409
- Cited by
- 216
- References
- 70
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 11 · 2023: 6 · 2022: 11 · 2021: 18 · 2020: 7 · 2019: 16 · 2018: 9 · 2017: 16 · 2016: 8 · 2015: 6 · 2014: 5 · 2013: 10 · 2012: 5
- FWCI
- 0.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- RNA (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- David and Lucile Packard Foundation
- National Institutes of Health (5r01gm057500-03)
- National Institute of General Medical Sciences (GM559343, GM57500)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Physical Sciences › Chemistry › Organic Chemistry › Physical Organic Chemistry and Reaction Kinetics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- ribozymes, deoxyribozymes, RNA cleavage, catalytic rate enhancement
- MeSH terms
- Esterification, Hydrolysis, Oxygen, RNA, RNA, Catalytic, Hydroxyl Radical
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