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In vitro selection of RNA lectins: using combinatorial chemistry to interpret ribozyme evolution
S M Lato1, A R Boles, A D Ellington
1Department of Chemistry, Indiana University, Bloomington 47405, USA.
Chemistry & Biology
|May 1, 1995
Summary
The diversity of RNA molecules capable of binding aminoglycoside antibiotics suggests these sites may not indicate evolutionary relationships. Natural products likely evolved to recognize specific nucleic acid structures.
Area of Science:
- Molecular Biology
- Biochemistry
- Evolutionary Biology
Background:
- A hypothesis suggests ribosomal RNA and group I introns are evolutionarily related due to their shared ability to bind aminoglycoside antibiotics.
- This hypothesis relies on the assumption that RNA molecules have limited ways to form aminoglycoside-binding sites.
Purpose of the Study:
- To investigate the diversity of RNA structures capable of binding aminoglycoside antibiotics.
- To assess whether the presence of aminoglycoside-binding sites in RNA is a reliable indicator of evolutionary relatedness.
Main Methods:
- In vitro selection was employed to generate RNA molecules with high affinity and specificity for aminoglycosides.
- Sequence analysis was performed on the selected RNA molecules to understand the structural diversity of binding sites.
Main Results:
- In vitro selection yielded numerous distinct RNA sequences that bind aminoglycosides tightly and specifically.
- These artificially selected binding sites exhibit functional similarities to naturally occurring ones.
- Sequence analysis revealed a wide variety of structural solutions for creating effective aminoglycoside-binding sites in RNA.
Conclusions:
- The presence of aminoglycoside-binding sites on RNA may not be a reliable marker for evolutionary relatedness.
- Aminoglycosides, as natural products, likely evolved to exploit inherent sequence- and structure-specific recognition capabilities of nucleic acids.
- This recognition mechanism is analogous to how chemists design molecules like lexitropsins to target specific nucleic acid sequences.