Nonenzymatic, template-directed ligation of oligoribonucleotides is highly regioselective for the formation of 3′-5′ phosphodiester bonds
Abstract
We have found that nonenzymatic, template-directed ligation reactions of oligoribonucleotides display high selectivity for the formation of 3'-5' rather than 2'-5' phosphodiester bonds. Formation of the 3'-5'-linked product is favored regardless of the metal ion catalyst or the leaving group, and for several different ligation junction sequences. The degree of selectivity depends on the leaving group: the ratio of 3'-5'- to 2'-5'-linked products was 10-15:1 when the 5'-phosphate was activated as the imidazolide, and 60-80:1 when the 5'-phosphate was activated by the formation of a 5'-triphosphate. Comparison of oligonucleotide ligation reactions with previously characterized single nucleotide primer extension reactions suggests that the strong preference for 3'-5'-linkages in oligonucleotide ligation is primarily due to occurence of ligation within the context of an extended Watston-Crick duplex. The ability of RNA to correctly self-assemble by template-directed ligation is an intrinsic consequence of its chemical structure and need not be imposed by an external catalyst (i.e., an enzyme polymerase); RNA therefore provides a reasonable structural basis for a self-replicating system in a prebiological world.
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Template-directed ligation appears to be a general phenomenon, occurring with peptides, small molecules and nucleic acids, and it can greatly accelerate bond formation.
“Template-directed ligation appears to be a general phenomenon, occurring with peptides, small molecules and nucleic acids (49–51), and it can greatly accelerate bond formation (52–54).”
From Prebiotically plausible mechanisms increase compositional diversity of nucleic acid sequences (2012) · cites this paper as [53]
Cites
Oligoribonucleotide synthesis using T7 RNA polymerase and synthetic DNA templates.
Milligan, J., Groebe, D., Witherell, G. W., & Uhlenbeck, O. (1987) · Nucleic Acids Research · doi:10.1093/nar/15.21.8783 · Cited by 1,971 · see citing works
Isolation of New Ribozymes from a Large Pool of Random Sequences
Bartel, D. P., & Szostak, J. W. (1993) · Science · doi:10.1126/science.7690155 · Cited by 900 · see citing works
Self-citationPhysical Chemistry of the H 2 SO 4 /HNO 3 /H 2 O System: Implications for Polar Stratospheric Clouds
Molina, M. J., Zhang, R., Wooldridge, P. J., McMahon, J. R., Kim, J. E., Chang, H. Y., & Beyer, K. D. (1993) · Science · doi:10.1126/science.261.5127.1418 · Cited by 257 · see citing works
RNA catalysis and the origins of life
Orgel, L. E. (1986) · Journal of Theoretical Biology · doi:10.1016/s0022-5193(86)80149-7 · Cited by 252 · see citing works
Oligomerization of (guanosine 5′-phosphor)-2-methylimidazolide on poly(C)
Inoue, T., & Orgel, L. E. (1982) · Journal of Molecular Biology · doi:10.1016/0022-2836(82)90169-3 · Cited by 209 · see citing works
Hydrolytic stability of helical RNA: a selective advantage for the natural 3',5'-bond.
Usher, D. A., & McHale, A. H. (1976) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.73.4.1149 · Cited by 179 · see citing works
Preferential formation of (2'–5')-linked internucleotide bonds in non-enzymatic reactions
Lohrmann, R., & Orgel, L. E. (1978) · Tetrahedron · doi:10.1016/0040-4020(78)88129-0 · Cited by 160 · see citing works
Theta-Sensitive Cell and Erythropoiesis: Identification of a Defect in W / W v Anemic Mice
Wiktor-Jędrzejczak, W., Sharkie, S., Ahmed, A. A., Sell, K. W., & Santos, G. W. (1977) · Science · doi:10.1126/science.322288 · Cited by 128 · see citing works
Giannaris, P. A., & Damha, M. J. (1993) · Nucleic Acids Research · doi:10.1093/nar/21.20.4742 · Cited by 109 · see citing works
Catalysis of accurate poly(C)-directed synthesis of 3′-5′-linked oligoguanylates by Zn2+
Bridson, P. K., & Orgel, L. E. (1980) · Journal of Molecular Biology · doi:10.1016/0022-2836(80)90337-x · Cited by 102 · see citing works
Efficient catalysis of polycytidylic acid-directed oligoguanylate formation by Pb2+
Lohrmann, R., & Orgel, L. E. (1980) · Journal of Molecular Biology · doi:10.1016/0022-2836(80)90263-6 · Cited by 94 · see citing works
Early Chemical Evolution of Nucleic Acids: A Theoretical Model
Usher, D. A. (1977) · Science · doi:10.1126/science.583625 · Cited by 71 · see citing works
Template-directed synthesis of oligoadenylates catalyzed by Pb2+ ions
Sleeper, H. L., Lohrmann, R., & Orgel, L. E. (1979) · Journal of Molecular Evolution · doi:10.1007/bf01739480 · Cited by 50 · see citing works
The catalysis of nucleotide polymerization by compounds of divalent lead
Sleeper, H. L., & Orgel, L. E. (1979) · Journal of Molecular Evolution · doi:10.1007/bf01732030 · Cited by 49 · see citing works
Heteropolynucleotides as templates for non-enzymatic polymerizations
Ninio, J., & Orgel, L. E. (1978) · Journal of Molecular Evolution · doi:10.1007/bf01733260 · Cited by 48 · see citing works
Studies of oligoadenylate formation on a poly(U) template
Lohrmann, R., & Orgel, L. E. (1979) · Journal of Molecular Evolution · doi:10.1007/bf01732341 · Cited by 35 · see citing works
Self-condensation of activated dinucleotides on polynucleotide templates with alternating sequences
Lohrmann, R., & Orgel, L. E. (1979) · Journal of Molecular Evolution · doi:10.1007/bf01732491 · Cited by 20 · see citing works
Condensation of activated diguanylates on a poly(C) template
Lohrmann, R., Bridson, P. K., & Orgel, L. E. (1981) · Journal of Molecular Evolution · doi:10.1007/bf01795752 · Cited by 13 · see citing works
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Prebiotic chemistry and the origin of the RNA world.
Leslie E., O. (2004) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409230490460765 · Cited by 1,124 · see citing works
Prebiotic Systems Chemistry: New Perspectives for the Origins of Life
Ruiz-Mirazo, K., Briones, C., & de la Escosura, A. (2014) · Chemical Reviews · doi:10.1021/cr2004844 · Cited by 930 · see citing works
Robertson, M. P., & Joyce, G. F. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a003608 · Cited by 556 · see citing works
One sequence, two ribozymes: implications for the emergence of new ribozyme folds
Schultes, E. A., & Bartel, D. P. (2000) · Science · doi:10.1126/science.289.5478.448 · Cited by 364 · see citing works
Self-citationThe eightfold path to non-enzymatic RNA replication
Szostak, J. W. (2012) · Journal of Systems Chemistry · doi:10.1186/1759-2208-3-2 · Cited by 359 · see citing works
Self-citationProgress Toward Synthetic Cells
Blain, J. C., & Szostak, J. W. (2014) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-080411-124036 · Cited by 314 · see citing works
Self-citationSchrum, J. P., Zhu, T. F., & Szostak, J. W. (2010) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a002212 · Cited by 255 · see citing works
Self-citationOpinion: Studies on the origin of life — the end of the beginning
Sutherland, J. D. (2017) · Nature Reviews Chemistry · doi:10.1038/s41570-016-0012 · Cited by 225 · see citing works
The Origin and Nature of Life on Earth: The Emergence of the Fourth Geosphere
Smith, E., & Morowitz, H. J. (2016) · doi:10.1017/cbo9781316348772 · Cited by 215 · see citing works
Genetics first or metabolism first? The formamide clue
Saladino, R., Botta, G., Pino, S., Costanzo, G., & Di Mauro, E. (2012) · Chemical Society Reviews · doi:10.1039/c2cs35066a · Cited by 215 · see citing works
The origin of the RNA world: Co-evolution of genes and metabolism
Copley, S. D., Smith, E., & Morowitz, H. J. (2007) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2007.08.001 · Cited by 184 · see citing works
Monnard, P.-A., Kanavarioti, A., & Deamer, D. W. (2003) · Journal of the American Chemical Society · doi:10.1021/ja036465h · Cited by 159 · see citing works
An optimal degree of physical and chemical heterogeneity for the origin of life?
Szostak, J. W. (2011) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2011.0140 · Cited by 133 · see citing works
Self-citationGeneration of Long RNA Chains in Water
Costanzo, G., Pino, S., Ciciriello, F., & Mauro, E. D. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.041905 · Cited by 126 · see citing works
The effect of cytidine on the structure and function of an RNA ligase ribozyme
Rogers, J., & Joyce, G. F. (2001) · RNA · doi:10.1017/s135583820100228x · Cited by 118 · see citing works
Prebiotically plausible oligoribonucleotide ligation facilitated by chemoselective acetylation
Bowler, F. R., Chan, C. K. W., Duffy, C. D., Gerland, B., Islam, S., Powner, M. W., Sutherland, J. D., & Xu, J. (2013) · Nature Chemistry · doi:10.1038/nchem.1626 · Cited by 108 · see citing works
Functional RNAs exhibit tolerance for non-heritable 2’-5’ versus 3’-5’ backbone heterogeneity
Engelhart, A. E., Powner, M. W., & Szostak, J. W. (2013) · Nature Chemistry · doi:10.1038/nchem.1623 · Cited by 107 · see citing works
Self-citationThe joys of in vitro selection: chemically dressing oligonucleotides to satiate protein targets
Eaton, B. E. (1997) · Current Opinion in Chemical Biology · doi:10.1016/s1367-5931(97)80103-2 · Cited by 106 · see citing works
A complex ligase ribozyme evolved in vitro from a group I ribozyme domain
Jaeger, L., Wright, M. C., & Joyce, G. F. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.26.14712 · Cited by 102 · see citing works
Rapid oligonucleotide-templated fluorogenic tetrazine ligations
Šečkutė, J., Yang, J., & Devaraj, N. K. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt540 · Cited by 95 · see citing works
Catalytic Synthesis of Polyribonucleic Acid on Prebiotic Rock Glasses
Jerome, C. A., Kim, H., Mojzsis, S. J., Benner, S. A., & Biondi, E. (2022) · Astrobiology · doi:10.1089/ast.2022.0027 · Cited by 90 · see citing works
HPLC methods for purity evaluation of man-made single-stranded RNAs
Kanavarioti, A. (2019) · Scientific Reports · doi:10.1038/s41598-018-37642-z · Cited by 83 · see citing works
Prebiotically plausible mechanisms increase compositional diversity of nucleic acid sequences
Derr, J., Manapat, M. L., Rajamani, S., Leu, K., Xulvi-Brunet, R., Joseph, I., Nowak, M. A., & Chen, I. A. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks065 · Cited by 74 · see citing works
In Search of an RNA Replicase Ribozyme
McGinness, K. E., & Joyce, G. F. (2003) · Chemistry & Biology · doi:10.1016/s1074-5521(03)00003-6 · Cited by 74 · see citing works
Phosphorylation of Adenosine with Trimetaphosphate Under Simulated Prebiotic Conditions
Cheng, C., Fan, C., Wan, R., Tong, C.-Y., Miao, Z., Chen, J., & Zhao, Y. (2002) · Origins of Life and Evolution of Biospheres · doi:10.1023/a:1016513114799 · Cited by 64 · see citing works
Efficient Solid-Phase Chemical Synthesis of 5′-Triphosphates of DNA, RNA, and their Analogues
Zlatev, I., Lavergne, T., Debart, F., Vasseur, J., Manoharan, M., & Morvan, F. (2010) · Organic Letters · doi:10.1021/ol1004214 · Cited by 63 · see citing works
Generation of RNA Molecules by a Base‐Catalysed Click‐Like Reaction
Costanzo, G., Saladino, R., Botta, G., Giorgi, A., Scipioni, A., Pino, S., & Di Mauro, E. (2012) · ChemBioChem · doi:10.1002/cbic.201200068 · Cited by 62 · see citing works
Pyranosyl‐RNA: Further Observations on Replication
Bolli, M. H., Micura, R., Pitsch, S., & Eschenmoser, A. (1997) · Helvetica Chimica Acta · doi:10.1002/hlca.19970800613 · Cited by 62 · see citing works
Enzyme-free ligation of dimers and trimers to RNA primers
Sosson, M., Pfeffer, D., & Richert, C. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz160 · Cited by 58 · see citing works
The Emergence of RNA from the Heterogeneous Products of Prebiotic Nucleotide Synthesis
Kim, S. C., O’Flaherty, D. K., Giurgiu, C., Zhou, L., & Szostak, J. W. (2021) · Journal of the American Chemical Society · doi:10.1021/jacs.0c12955 · Cited by 55 · see citing works
Self-citationA Stochastic Model of Nonenzymatic Nucleic Acid Replication: “Elongators” Sequester Replicators
Fernando, C., von Kiedrowski, G., & Szathmáry, E. (2007) · Journal of Molecular Evolution · doi:10.1007/s00239-006-0218-4 · Cited by 52 · see citing works
Efficient One‐Step Synthesis of Biologically Related Lariat RNAs by a Deoxyribozyme
Wang, Y., & Silverman, S. K. (2005) · Angewandte Chemie International Edition · doi:10.1002/anie.200501643 · Cited by 52 · see citing works
Landweber, L. F., & Pokrovskaya, I. D. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.1.173 · Cited by 52 · see citing works
Structural insights into the effects of 2’-5’ linkages on the RNA duplex
Sheng, J., Li, L., Engelhart, A. E., Gan, J., Wang, J., & Szostak, J. W. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1317799111 · Cited by 50 · see citing works
Self-citationTamura, K. (2008) · Biosystems · doi:10.1016/j.biosystems.2007.12.005 · Cited by 49 · see citing works
In vitro Selection of Chemically Modified DNAzymes
Huang, P. J., & Liu, J. (2020) · ChemistryOpen · doi:10.1002/open.202000134 · Cited by 48 · see citing works
A Threose Nucleic Acid Enzyme with RNA Ligase Activity
Wang, Y., Wang, Y., Song, D., Sun, X., Zhang, Z., Li, X., Li, Z., & Yu, H. (2021) · Journal of the American Chemical Society · doi:10.1021/jacs.1c02895 · Cited by 48 · see citing works
Genotype network intersections promote evolutionary innovation
Bendixsen, D. P., Collet, J., Østman, B., & Hayden, E. J. (2019) · PLoS Biology · doi:10.1371/journal.pbio.3000300 · Cited by 47 · see citing works
Nonenzymatic Polymerization into Long Linear RNA Templated by Liquid Crystal Self-Assembly
Todisco, M., Fraccia, T. P., Smith, G. P., Corno, A., Bethge, L., Klußmann, S., Paraboschi, E. M., Asselta, R., Colombo, D., Zanchetta, G., et al. (2018) · ACS Nano · doi:10.1021/acsnano.8b05821 · Cited by 46 · see citing works
Non‐Enzymatic Assembly of a Minimized RNA Polymerase Ribozyme
Wachowius, F., & Holliger, P. (2019) · ChemSystemsChem · doi:10.1002/syst.201900004 · Cited by 46 · see citing works
Conversion of a Ribozyme to a Deoxyribozyme through In Vitro Evolution
Paul, N., Springsteen, G., & Joyce, G. F. (2006) · Chemistry & Biology · doi:10.1016/j.chembiol.2006.01.007 · Cited by 43 · see citing works
Zn 2+ -Dependent Deoxyribozymes That Form Natural and Unnatural RNA Linkages
Manthei, K. A., Purtha, W. E., Wolf, A. C., Flynn-Charlebois, A., & Silverman, S. K. (2005) · Biochemistry · doi:10.1021/bi050146g · Cited by 43 · see citing works
Goldilocks and RNA: where Mg2+ concentration is just right
Guth-Metzler, R., Mohamed, A. M., Cowan, E. T., Henning, A., Ito, C., Frenkel‐Pinter, M., Wartell, R. M., Glass, J. B., & Williams, L. D. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad124 · Cited by 37 · see citing works
From the one-carbon amide formamide to RNA all the steps are prebiotically possible
Saladino, R., Botta, G., Pino, S., Costanzo, G., & Mauro, E. D. (2012) · Biochimie · doi:10.1016/j.biochi.2012.02.018 · Cited by 37 · see citing works
Desulfurization Activated Phosphorothioate DNAzyme for the Detection of Thallium
Huang, P. J., Vazin, M., & Liu, J. (2015) · Analytical Chemistry · doi:10.1021/acs.analchem.5b02568 · Cited by 37 · see citing works
Deep sequencing of non-enzymatic RNA primer extension
Duzdevich, D., Carr, C. E., & Szostak, J. W. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa400 · Cited by 37 · see citing works
Self-citationCzárán, T., Könnyű, B., & Szathmáry, E. (2015) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2015.06.002 · Cited by 37 · see citing works
Monnard, P., & Ziock, H. J. (2008) · Chemistry & Biodiversity · doi:10.1002/cbdv.200890141 · Cited by 36 · see citing works
From Formamide to RNA, the Path Is Tenuous but Continuous
Pino, S., Šponer, J. E., Costanzo, G., Saladino, R., & Mauro, E. D. (2015) · Life · doi:10.3390/life5010372 · Cited by 33 · see citing works
Šponer, J. E., Šponer, J., Giorgi, A., Mauro, E. D., Pino, S., & Costanzo, G. (2015) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.5b00601 · Cited by 33 · see citing works
Duzdevich, D., Carr, C. E., Ding, D., Zhang, S. J., Walton, T., & Szostak, J. W. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab173 · Cited by 33 · see citing works
Self-citationTupper, A. S., & Higgs, P. G. (2021) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2021.110822 · Cited by 32 · see citing works
Kurz, M., Göbel, K., Hartel, C., & Göbel, M. (1997) · Angewandte Chemie International Edition in English · doi:10.1002/anie.199708421 · Cited by 31 · see citing works
Non‐Enzymatic RNA Backbone Proofreading through Energy‐Dissipative Recycling
Mariani, A., & Sutherland, J. D. (2017) · Angewandte Chemie International Edition · doi:10.1002/anie.201703169 · Cited by 30 · see citing works
The Role of Templating in the Emergence of RNA from the Prebiotic Chemical Mixture
Tupper, A. S., Shi, K. Y., & Higgs, P. G. (2017) · Life · doi:10.3390/life7040041 · Cited by 30 · see citing works
Xylonucleic acid: synthesis, structure, and orthogonal pairing properties
Maiti, M., Maiti, M., Knies, C., Dumbre, S. G., Lescrinier, E., Rosemeyer, H., Ceulemans, A. J., & Herdewijn, P. A. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv719 · Cited by 30 · see citing works
Walton, T., DasGupta, S., Duzdevich, D., Oh, S. S., & Szostak, J. W. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1914367117 · Cited by 30 · see citing works
Self-citationAcridine‐Labeled Primers as Tools for the Study of Nonenzymatic RNA Oligomerization
Kurz, M., Göbel, K., Hartel, C., & Göbel, M. (1998) · Helvetica Chimica Acta · doi:10.1002/hlca.19980810528 · Cited by 27 · see citing works
High-Fidelity RNA Copying via 2′,3′-Cyclic Phosphate Ligation
Serrão, A. C., Wunnava, S., Dass, A. V., Ufer, L., Schwintek, P., Mast, C. B., & Braun, D. (2024) · Journal of the American Chemical Society · doi:10.1021/jacs.3c10813 · Cited by 26 · see citing works
Polyphosphorylation and Non-Enzymatic Template-Directed Ligation of Oligonucleotides
Gao, K., & Orgel, L. E. (2000) · Origins of Life and Evolution of Biospheres · doi:10.1023/a:1006683507864 · Cited by 26 · see citing works
Könnyű, B., & Czárán, T. (2013) · BMC Evolutionary Biology · doi:10.1186/1471-2148-13-204 · Cited by 25 · see citing works
Monte Carlo simulation of early molecular evolution in the RNA World
Ma, W., Yu, C., & Zhang, W. (2006) · Biosystems · doi:10.1016/j.biosystems.2006.06.005 · Cited by 25 · see citing works
Chemical Primer Extension at Submillimolar Concentration of Deoxynucleotides
Röthlingshöfer, M., & Richert, C. (2010) · The Journal of Organic Chemistry · doi:10.1021/jo1002467 · Cited by 24 · see citing works
A Mechanistic Explanation for the Regioselectivity of Nonenzymatic RNA Primer Extension
Giurgiu, C., Li, L., O’Flaherty, D. K., Tam, C. P., & Szostak, J. W. (2017) · Journal of the American Chemical Society · doi:10.1021/jacs.7b08784 · Cited by 24 · see citing works
Self-citationSawai, H., Totsuka, S., Yamamoto, K., & Ozaki, H. (1998) · Nucleic Acids Research · doi:10.1093/nar/26.12.2995 · Cited by 24 · see citing works
Synthesis of 5′-NAD-Capped RNA
Höfer, K., Abele, F., Schlotthauer, J., & Jäschke, A. (2016) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.6b00072 · Cited by 23 · see citing works
Prebiotically Plausible “Patching” of RNA Backbone Cleavage through a 3′–5′ Pyrophosphate Linkage
Wright, T. H., Giurgiu, C., Zhang, W., Radakovic, A., O’Flaherty, D. K., Zhou, L., & Szostak, J. W. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.9b08237 · Cited by 22 · see citing works
Self-citationTemplate-Free Assembly of Functional RNAs by Loop-Closing Ligation
Wu, L.-F., Liu, Z., Roberts, S. J., Su, M., Szostak, J. W., & Sutherland, J. D. (2022) · Journal of the American Chemical Society · doi:10.1021/jacs.2c05601 · Cited by 21 · see citing works
Self-citationStructure-Guided Engineering of the Regioselectivity of RNA Ligase Ribozymes
Pitt, J. N., & Ferré-D’Amaré, A. R. (2009) · Journal of the American Chemical Society · doi:10.1021/ja8067325 · Cited by 21 · see citing works
Intramolecular RNA replicase: Possibly the first self-replicating molecule in the RNA world
Ma, W., & Yu, C. (2006) · Origins of Life and Evolution of Biospheres · doi:10.1007/s11084-005-9006-1 · Cited by 20 · see citing works
Recent Advances in Biocatalytic and Chemoenzymatic Synthesis of Oligonucleotides
Bizat, P. N., Sabat, N., & Hollenstein, M. (2025) · ChemBioChem · doi:10.1002/cbic.202400987 · Cited by 20 · see citing works
(2006) · Cited by 20 · see citing works
The nonenzymatic template-directed ligation of oligonucleotides
Lutay, A., Chernolovskaya, E. L., Аркадьевна, З. М., & Vlassov, V. V. (2006) · Biogeosciences · doi:10.5194/bg-3-243-2006 · Cited by 20 · see citing works
Chemical ligation of oligonucleotides using an electrophilic phosphorothioester
Maruyama, H., Oikawa, R., Hayakawa, M., Takamori, S., Kimura, Y., Abe, N., Tsuji, G., Matsuda, A., Shuto, S., Ito, Y., et al. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx459 · Cited by 19 · see citing works
Semlow, D. R., & Silverman, S. K. (2005) · Journal of Molecular Evolution · doi:10.1007/s00239-004-0326-y · Cited by 19 · see citing works
How To Form a Phosphate Anhydride Linkage in Nucleotide Derivatives
Sherstyuk, Y. V., & Abramova, T. V. (2015) · ChemBioChem · doi:10.1002/cbic.201500406 · Cited by 18 · see citing works
Prebiotic synthesis and triphosphorylation of 3′-amino-TNA nucleosides
Whitaker, D. E., & Powner, M. W. (2022) · Nature Chemistry · doi:10.1038/s41557-022-00982-5 · Cited by 18 · see citing works
An Efficient Lanthanide‐Dependent DNAzyme Cleaving 2′–5′‐Linked RNA
Zhou, W., Ding, J., & Liu, J. (2016) · ChemBioChem · doi:10.1002/cbic.201500690 · Cited by 18 · see citing works
Assembly‐driven protection from hydrolysis as key selective force during chemical evolution
Edri, R., Fisher, S., Menor-Salván, C. A., Williams, L. D., & Frenkel‐Pinter, M. (2023) · FEBS Letters · doi:10.1002/1873-3468.14766 · Cited by 16 · see citing works
Kanavarioti, A., Lee, L. F., & Gangopadhyay, S. (1999) · Origins of Life and Evolution of Biospheres · doi:10.1023/a:1006540607594 · Cited by 16 · see citing works
Kurz, M., Göbel, K., Hartel, C., & Göbel, M. W. (1997) · Angewandte Chemie · doi:10.1002/ange.19971090812 · Cited by 15 · see citing works
Chemistry on Nucleic Acid Templates
Berger, J., & Oberhuber, M. (2010) · Chemistry & Biodiversity · doi:10.1002/cbdv.201000108 · Cited by 15 · see citing works
Squaramides and Ureas: A Flexible Approach to Polymerase‐Compatible Nucleic Acid Assembly
Shivalingam, A., Taemaitree, L., El-Sagheer, A. H., & Brown, T. P. (2020) · Angewandte Chemie International Edition · doi:10.1002/anie.202000209 · Cited by 15 · see citing works
New evolutionary insights into the non‐enzymatic origin of RNA oligomers
Šponer, J. E., Šponer, J., & Mauro, E. D. (2016) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1400 · Cited by 15 · see citing works
Limited Sequence Diversity Within a Population Supports Prebiotic RNA Reproduction
Mizuuchi, R., & Lehman, N. (2019) · Life · doi:10.3390/life9010020 · Cited by 14 · see citing works
Nonenzymatic Template-Directed Condensation of Short-Chained Oligouridylates on a Poly(A) Template
Sawai, H., & Wada, M. (2000) · Origins of Life and Evolution of Biospheres · doi:10.1023/a:1026583814064 · Cited by 14 · see citing works
DasGupta, S., Weiss, Z., Nisler, C. R., & Szostak, J. W. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2407325121 · Cited by 13 · see citing works
Self-citationTam, C. P., Zhou, L., Fahrenbach, A. C., Zhang, W., Walton, T., & Szostak, J. W. (2017) · Journal of the American Chemical Society · doi:10.1021/jacs.7b11623 · Cited by 13 · see citing works
Self-citationLin, H., Jiménez, E. I., Arriola, J. T., Müller, U. F., & Krishnamurthy, R. (2021) · Angewandte Chemie International Edition · doi:10.1002/anie.202113625 · Cited by 13 · see citing works
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Bedau, M. A., Buchanan, A., Gazzola, G., Hanczyc, M. M., Maeke, T., McCaskill, J. S., Poli, I., & Packard, N. H. (2006) · Lecture notes in computer science · doi:10.1007/11740698_18 · Cited by 13 · see citing works
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Chen, H., Du, F., Chen, G., Streckenbach, F., Yasmeen, A., Zhao, Y. F., & Tang, Z. (2014) · Scientific Reports · doi:10.1038/srep04595 · Cited by 12 · see citing works
tRNA sequences can assemble into a replicator
Kühnlein, A., Lanzmich, S. A., & Braun, D. (2021) · eLife · doi:10.7554/elife.63431 · Cited by 12 · see citing works
Sawai, H., Wada, M., Kouda, T., & Ozaki, A. (2006) · ChemBioChem · doi:10.1002/cbic.200500291 · Cited by 12 · see citing works
Efficient One‐Step Synthesis of Biologically Related Lariat RNAs by a Deoxyribozyme
Wang, Y., & Silverman, S. K. (2005) · Angewandte Chemie · doi:10.1002/ange.200501643 · Cited by 12 · see citing works
Virta, P. (2025) · Nucleic Acids Research · doi:10.1093/nar/gkaf1084 · Cited by 11 · see citing works
Structural insights into RNA duplexes with multiple 2′-5′-linkages
Shen, F., Luo, Z., Liu, H., Wang, R., Zhang, S., Gan, J., & Sheng, J. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw1307 · Cited by 11 · see citing works
Structure and selection in an autocatalytic binary polymer model
Tanaka, S., Fellermann, H., & Rasmussen, S. (2014) · Europhysics Letters (EPL) · doi:10.1209/0295-5075/107/28004 · Cited by 11 · see citing works
Non-enzymatic recombination of RNA: Ligation in loops
Staroseletz, Y., Nechaev, S., Bichenkova, E. V., Bryce, R. A., Watson, C., Vlassov, V. V., & Аркадьевна, З. М. (2017) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2017.10.019 · Cited by 11 · see citing works
A Threose Nucleic Acid (TNA) Enzyme Catalyzing Native 3′-5′ Ligation of RNA
Wang, J., Han, F., Zou, Y., Wang, M., Wang, Y., Chen, J., & Yu, H. (2025) · Journal of the American Chemical Society · doi:10.1021/jacs.5c07235 · Cited by 10 · see citing works
Saraya, J. S., Horton, N. G., Capperauld, M. J., Zakaria, E., & O’Flaherty, D. K. (2025) · Chemistry - An Asian Journal · doi:10.1002/asia.202500537 · Cited by 9 · see citing works
- Authors
- Rohatgi, R., Bartel, D. P., & Szostak, J. W.
- Affiliations
- Massachusetts General Hospital (US)
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 1996-01-01
- Volume
- 118
- Issue
- 14
- Pages
- 3340-3344
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- OpenAlex
- W1979795987
- Cited by
- 134
- References
- 18
- Citations by year
- 2025: 13 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 8 · 2020: 6 · 2019: 8 · 2018: 2 · 2017: 9 · 2016: 6 · 2015: 7 · 2014: 5 · 2013: 5 · 2012: 8
- FWCI
- 3.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the American Chemical Society (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Division of Chemistry
- Topics
- Physical Sciences › Physics and Astronomy › Astronomy and Astrophysics › Origins and Evolution of Life
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- template-directed ligation, oligoribonucleotides, regioselectivity, metal ion catalysis, leaving group effects, 5'-triphosphate, imidazolides, RNA self-assembly, RNA primers
- MeSH terms
- Base Sequence, Hydrolysis, Imidazoles, Kinetics, Molecular Sequence Data, Nucleotides, Oligonucleotides, Oligoribonucleotides, RNA, Structure-Activity Relationship, Templates, Genetic, Time Factors, RNA, Catalytic, Evolution, Molecular
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