In vitro selected GUAA tetraloop-binding receptors with structural plasticity and evolvability towards natural RNA structural modules
| Autor: | Erin R. Calkins, Gurkeerat Singh, Yi-Ling Kao, Luc Jaeger, Paul Zakrevsky, Stéphanie Baudrey, Vasken L Keleshian |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Models
Molecular 0303 health sciences AcademicSubjects/SCI00010 RNA Robustness (evolution) Computational biology Biology 010402 general chemistry 01 natural sciences Tetraloop Ribosome 0104 chemical sciences Macromolecular assembly Evolvability 03 medical and health sciences Structural Biology Mutagenesis Genetics Epistasis Nucleic Acid Conformation Directed Molecular Evolution Receptor 030304 developmental biology |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | GNRA tetraloop-binding receptor interactions are key components in the macromolecular assembly of a variety of functional RNAs. In nature, there is an apparent bias for GAAA/11nt receptor and GYRA/helix interactions, with the former interaction being thermodynamically more stable than the latter. While past in vitro selections allowed isolation of novel GGAA and GUGA receptors, we report herein an in vitro selection that revealed several novel classes of specific GUAA receptors with binding affinities comparable to those from natural GAAA/11nt interactions. These GUAA receptors have structural homology with double-locked bulge RNA modules naturally occurring in ribosomal RNAs. They display mutational robustness that enables exploration of the sequence/phenotypic space associated to GNRA/receptor interactions through epistasis. Their thermodynamic self-assembly fitness landscape is characterized by a rugged neutral network with possible evolutionary trajectories toward natural GNRA/receptor interactions. High throughput sequencing analysis revealed synergetic mutations located away from the tertiary interactions that positively contribute to assembly fitness. Our study suggests that the repertoire of GNRA/receptor interactions is much larger than initially thought from the analysis of natural stable RNA molecules and also provides clues for their evolution towards natural GNRA/receptors. |
| Databáze: | OpenAIRE |
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