Polymerase ribozyme efficiency increased by G/T-rich DNA oligonucleotides
Open accessAbstract
The RNA world hypothesis states that the early evolution of life went through a stage where RNA served as genome and as catalyst. The replication of RNA world organisms would have been facilitated by ribozymes that catalyze RNA polymerization. To recapitulate an RNA world in the laboratory, a series of RNA polymerase ribozymes was developed previously. However, these ribozymes have a polymerization efficiency that is too low for self-replication, and the most efficient ribozymes prefer one specific template sequence. The limiting factor for polymerization efficiency is the weak sequence-independent binding to its primer/template substrate. Most of the known polymerase ribozymes bind an RNA heptanucleotide to form the P2 duplex on the ribozyme. By modifying this heptanucleotide, we were able to significantly increase polymerization efficiency. Truncations at the 3′-terminus of this heptanucleotide increased full-length primer extension by 10-fold, on a specific template sequence. In contrast, polymerization on several different template sequences was improved dramatically by replacing the RNA heptanucleotide with DNA oligomers containing randomized sequences of 15 nt. The presence of G and T in the random sequences was sufficient for this effect, with an optimal composition of 60% G and 40% T. Our results indicate that these DNA sequences function by establishing many weak and nonspecific base-pairing interactions to the single-stranded portion of the template. Such low-specificity interactions could have had important functions in an RNA world.
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G/T-rich DNA sequences improve the efficiency of an RNA polymerase ribozyme, presumably by increasing non-specific associations.
“G/T-rich DNA sequences improve the efficiency of an RNA polymerase ribozyme, presumably by increasing non-specific associations (Yao and Muller 2011).”
From The paradox of dual roles in the RNA world: resolving the conflict between stable folding and templating ability (2013) · cites this paper as Yao and Muller 2011
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Ivica, N. A., Obermayer, B., Campbell, G. W., Rajamani, S., Gerland, U., & Chen, I. A. (2013) · Journal of Molecular Evolution · doi:10.1007/s00239-013-9584-x · Cited by 42 · see citing works
- Authors
- Yao, C., & Müller, U. F.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Müller, Ulrich F.
- Venue
- RNA
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2011-05-27
- Volume
- 17
- Issue
- 7
- Pages
- 1274-1281
- ISSN
- 1355-8382 (ISSN-L)
- 1469-9001
- PMC
- PMC3138564
- OpenAlex
- W2107057327
- Cited by
- 8
- References
- 25
- Citations by year
- 2021: 1 · 2018: 1 · 2015: 2 · 2014: 1 · 2013: 1 · 2012: 1
- FWCI
- 0.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- RNA (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Science Foundation (0743985)
- 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
- RNA world, self-replication, origin of life, RNA catalysis
- MeSH terms
- Base Composition, Base Sequence, DNA, DNA-Directed DNA Polymerase, Efficiency, Molecular Sequence Data, Nucleic Acid Conformation, Oligonucleotides, Substrate Specificity, Templates, Genetic, Protein Engineering, RNA, Catalytic
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