Cited by 134Origins and Evolution of LifeRNA and protein synthesis mechanismsDNA and Nucleic Acid Chemistry

Nonenzymatic, template-directed ligation of oligoribonucleotides is highly regioselective for the formation of 3′-5′ phosphodiester bonds

Rohatgi, Rajat, Bartel, David P., Szostak, Jack W.·1996·Journal of the American Chemical Society

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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Crossref · 10.1021/ja9537134

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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).”

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Authors
Rohatgi, R., Bartel, D. P., & Szostak, J. W.
Affiliations
Massachusetts General Hospital (US)
Venue
Journal of the American Chemical Society
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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