Rapid and simple ribozymic aminoacylation using three conserved nucleotides
Open accessAbstract
Selection-amplification finds new RNA enzymes (ribozymes) among randomized RNAs with flanking unvaried sequences (primer complements). Precise removal of 3'-primer before reaction selected aminoacylation from PheAMP in three cycles, yielding active RNAs (k(cat) = 12-20 min(-1)) using only three conserved nucleotides, acting independently of divalent ions. This unusually simple RNA active site encouraged study of the reaction via molecular mechanics-based free energy minimization. On this basis, we suggest a chemical path for RNA-catalyzed transaminoacylation. Site modeling also predicted new features, L-stereoselectivity, 2'-regioselectivity, independence of amino acid side chain, and phosphorylated activating group, that were subsequently verified. The same selection also showed that RNA aminoacylation from adenylate is simpler than from CoA thioester, potentially rationalizing translational activation by adenylates. The simplicity of this active site suggests a general route to small ribozymes.
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Since ligation does not require a long ribozyme sequence, it is template binding and daughter-strand separation that necessitate the help of more complex and longer RNA polymerase ribozymes.
“Since ligation does not require a long ribozyme sequence [108], it is template binding and daughter-strand separation that necessitate the help of more complex and longer RNA polymerase ribozymes.”
From Ecology and Evolution in the RNA World Dynamics and Stability of Prebiotic Replicator Systems (2017) · cites this paper as [108]
The Selection scheme describes ligating an oligonucleotide to selected RNAs for amplification, but does not say that RNA-catalyzed ligation requires only a short ribozyme sequence. The Discussion concerns the small active site of an aminoacylation ribozyme, not a ligation ribozyme. Searches for short ligation ribozymes and for template binding and daughter-strand separation found no passage establishing the cited clause. (LLM, conf=0.75)
Experimental — accuracy not yet measuredArtificial selections have identified ribozymes capable of aminoacylating their own sequence or other sequences (and tRNAs) in trans at specific sites, using a variety of activated amino acids or modified precursors.
“Artificial selections have identified ribozymes capable of aminoacylating their own sequence or other sequences (and tRNAs) in trans at specific sites, using a variety of activated amino acids or modified precursors (Figure 3A) [180–185].”
From The RNA world as a model system to study the origin of life (2015) · cites this paper as [180]
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“Since ligation does not require a long ribozyme sequence [108], it is template binding and daughter-strand separation that necessitate the help of more complex and longer RNA polymerase ribozymes.”
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- Authors
- Chumachenko, N. V., Novikov, Y., & Yarus, M.
- Affiliations
- University of Colorado Boulder (US)
- Corresponding author
- Yarus, M.
- ORCID
- Yarus, M.
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2009-03-24
- Volume
- 131
- Issue
- 14
- Pages
- 5257-5263
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- PMC
- PMC2750092
- OpenAlex
- W2061052380
- Cited by
- 68
- References
- 34
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 6 · 2022: 3 · 2021: 3 · 2020: 8 · 2019: 3 · 2018: 2 · 2017: 7 · 2016: 5 · 2015: 4 · 2014: 3 · 2013: 3 · 2012: 4
- FWCI
- 1.61
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of the American Chemical Society (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (R01 GM48080, R01GM048080)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Physical Sciences › Physics and Astronomy › Astronomy and Astrophysics › Origins and Evolution of Life
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- conserved nucleotides, free energy minimization
- MeSH terms
- Models, Molecular, Nucleic Acid Conformation, Nucleotides, Stereoisomerism, RNA, Catalytic, Catalytic Domain, Aminoacylation, SELEX Aptamer Technique
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