ArticleNucleic acids research2014
Next-generation sequencing reveals how RNA catalysts evolve from random space.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Generating experimentally unrelated target molecule-binding highly functionalized nucleic-acid polymers using machine learning.Nature communications · 2022Article
- Self-Reproduction and Darwinian Evolution in Autocatalytic Chemical Reaction Systems.Life (Basel, Switzerland) · 2021Review
- Phased nucleotide inserts for sequencing low-diversity RNA samples from in vitro selection experiments.RNA (New York, N.Y.) · 2020Article
- Comprehensive sequence-to-function mapping of cofactor-dependent RNA catalysis in the glmS ribozyme.Nature communications · 2020Article
- Systematic minimization of RNA ligase ribozyme through large-scale design-synthesis-sequence cycles.Nucleic acids research · 2019Article
- A Novel Small RNA-Cleaving Deoxyribozyme with a Short Binding Arm.Scientific reports · 2019Article
- Analysis of in vitro evolution reveals the underlying distribution of catalytic activity among random sequences.Nucleic acids research · 2017Article
- Recognizing RNA structural motifs in HT-SELEX data for ribosomal protein S15.BMC bioinformatics · 2017Article
- Viroid quasispecies revealed by deep sequencing.RNA biology · 2017Article
- Synthetic, Switchable Enzymes.Journal of molecular microbiology and biotechnology · 2017Review
- High-Throughput Mutational Analysis of a Twister Ribozyme.Angewandte Chemie (International ed. in English) · 2016Article
- Searching for a DNAzyme Version of the Leadzyme.Journal of molecular evolution · 2015Article
- Elucidating the molecular architecture of adaptation via evolve and resequence experiments.Nature reviews. Genetics · 2015Review
- Fitness Landscapes of Functional RNAs.Life (Basel, Switzerland) · 2015Review
- In vitro evolution of distinct self-cleaving ribozymes in diverse environments.Nucleic acids research · 2015Article
- High-throughput assay and engineering of self-cleaving ribozymes by sequencing.Nucleic acids research · 2015Article
- FASTAptamer: A Bioinformatic Toolkit for High-throughput Sequence Analysis of Combinatorial Selections.Molecular therapy. Nucleic acids · 2015Article
- Broccoli: rapid selection of an RNA mimic of green fluorescent protein by fluorescence-based selection and directed evolution.Journal of the American Chemical Society · 2014Article
- A synthetic approach to abiogenesis.Nature methods · 2014Article
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4 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Catalytic RNAs are attractive objects for studying molecular evolution. To understand how RNA libraries can evolve from randomness toward highly active catalysts, we analyze the original samples that led to the discovery of Diels-Alderase ribozymes by next-generation sequencing. Known structure-activity relationships are used to correlate abundance with catalytic performance. We find that efficient catalysts arose not just from selection for reactivity among the members of the starting library, but from improvement of less potent precursors by mutations. We observe changes in the ribozyme population in response to increasing selection pressure. Surprisingly, even after many rounds of enrichment, the libraries are highly diverse, suggesting that potential catalysts are more abundant in random space than generally thought. To highlight the use of next-generation sequencing as a tool for in vitro selections, we also apply this technique to a recent, less characterized ribozyme selection. Making use of the correlation between sequence evolution and catalytic activity, we predict mutations that improve ribozyme activity and validate them biochemically. Our study reveals principles underlying ribozyme in vitro selections and provides guidelines to render future selections more efficient, as well as to predict the conservation of key structural elements, allowing the rational improvement of catalysts.
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