Witnessing the structural evolution of an RNA enzyme
| Autor: | Yu-Ting Huang, David P. Horning, Gerald F. Joyce, Xavier Portillo, Ronald R. Breaker |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
QH301-705.5
Protein Conformation Science Population Mutagenesis (molecular biology technique) Biology General Biochemistry Genetics and Molecular Biology Catalysis Evolution Molecular ribozyme Structure-Activity Relationship chemistry.chemical_compound Molecular evolution Catalytic Domain RNA polymerase RNA Catalytic Biology (General) education Phylogeny Polymerase education.field_of_study General Immunology and Microbiology Phylogenetic tree molecular evolution General Neuroscience Ribozyme RNA General Medicine DNA-Directed RNA Polymerases Directed evolution chemistry Evolutionary biology Mutation biology.protein Medicine Nucleic Acid Conformation Directed Molecular Evolution |
| Zdroj: | eLife, Vol 10 (2021) |
| DOI: | 10.1101/2021.06.22.449496 |
| Popis: | An RNA polymerase ribozyme that has been the subject of extensive directed evolution efforts has attained the ability to synthesize complex functional RNAs, including a full-length copy of its own evolutionary ancestor. During the course of evolution, the catalytic core of the ribozyme has undergone a major structural rearrangement, resulting in a novel tertiary structural element that lies in close proximity to the active site. Through a combination of site-directed mutagenesis, structural probing, and deep sequencing analysis, the trajectory of evolution was seen to involve the progressive stabilization of the new structure, which provides the basis for improved catalytic activity of the ribozyme. Multiple paths to the new structure were explored by the evolving population, converging upon a common solution. Tertiary structural remodeling of RNA is known to occur in nature, as evidenced by the phylogenetic analysis of extant organisms, but this type of structural innovation had not previously been observed in an experimental setting. Despite prior speculation that the catalytic core of the ribozyme had become trapped in a narrow local fitness optimum, the evolving population has broken through to a new fitness locale, suggesting that further improvement of polymerase activity may be achievable. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|