Cited by 30RNA and protein synthesis mechanismsDNA and Nucleic Acid ChemistryOrigins and Evolution of Life

Substrate 2′-Hydroxyl Groups Required for Ribozyme-Catalyzed Polymerization

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Müller, Ulrich F., Bartel, David P.·2003·Chemistry & Biology

Abstract

A polymerase ribozyme has been generated that uses nucleoside triphosphates to elongate an RNA primer by the successive addition of nucleotides complementary to an RNA template. Its polymerization is accurate, with an average error rate less than 3%, and it is general in terms of the sequence and the length of the primer and template RNAs. To begin to understand how the substrate contacts contribute to this accurate and general activity, we investigated which primer and template 2'-hydroxyl groups are involved in substrate recognition. We identified eight positions where 2'-deoxy substitutions can influence polymerization kinetics. All eight are within five nucleotides of the primer 3' terminus. Some, but not all, of the 2'-deoxy effects appear to be sequence dependent. These results begin to build a picture of how the polymerase ribozyme recognizes its substrates.

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Crossref · 10.1016/s1074-5521(03)00171-6

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  • The crystal structure of the Class I RNA ligase suggests that this linker sequence is positioned to interact with the downstream RNA template and could strengthen the ribozyme's sequence-general contacts with the upstream duplex, enhancing primer/template binding.

    “Examination of the crystal structure of the Class I RNA ligase29,30, from which the catalytic core of the ribozyme polymerase is derived, suggests this sequence is well-positioned to interact with the downstream RNA template (Fig. 3a), and could augment the sequence-general contacts the ribozyme makes with the upstream duplex16,29,31 to enhance primer/template binding.”

    From In-ice evolution of RNA polymerase ribozyme activity (2013) · cites this paper as [31]

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Authors
Müller, U. F., & Bartel, D. P.
Affiliations
Whitehead Institute for Biomedical Research (US)
Corresponding author
Bartel, David P.
Venue
Chemistry & Biology
Publisher
Elsevier BV
Published
2003-09
Volume
10
Issue
9
Pages
799-806
ISSN
1074-5521 (ISSN-L)
OpenAlex
W2078089564
Cited by
30
References
48
Citations by year
2026: 1 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 1 · 2019: 2 · 2018: 3 · 2017: 1 · 2015: 1 · 2013: 4
FWCI
0.46
Type
journal article
Language
en
Open access
Locations
  • Chemistry & Biology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of General Medical Sciences (R01-GM61835, R01GM061835)
Topics
  • 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
  • Physical Sciences › Physics and Astronomy › Astronomy and Astrophysics › Origins and Evolution of Life
Keywords
RNA polymerization, 2'-hydroxyl group, substrate recognition, nucleoside triphosphates, polymerization kinetics, sequence dependence, RNA template, RNA primers
MeSH terms
Catalysis, Kinetics, RNA, RNA Nucleotidyltransferases, RNA, Double-Stranded, Structure-Activity Relationship, Substrate Specificity, Templates, Genetic, RNA, Catalytic, Hydroxyl Radical

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