In vitro selection of RNA lectins: using combinatorial chemistry to interpret ribozyme evolution.
BACKGROUND
It has been hypothesized that the fact that both ribosomal RNA and the group I intron can bind to aminoglycoside antibiotics implies that these RNAs are evolutionarily related. This hypothesis requires the assumption that there are relatively few ways for RNA molecules to form aminoglycoside-binding sites.


RESULTS
We have used in vitro selection to determine the diversity of aminoglycoside-binding sites that can be formed by RNA molecules. We have generated RNA 'lectins' that can bind aminoglycosides tightly and specifically. Sequence analysis indicates that there are many different ways to form tight and specific aminoglycoside binding sites. These artificially selected binding sites are functionally similar to those that have arisen from natural selection.


CONCLUSIONS
Our results suggest that the presence of aminoglycoside-binding sites on RNA molecules may not be a useful trait for determining evolutionary relatedness. Instead, the fact that RNA molecules can bind these 'low molecular-weight effectors' may indicate that natural products such as aminoglycosides have evolved to exploit sequence- and structure-specific recognition of nucleic acids, in much the same way that lexitropsins have been designed by chemists to recognise specific nucleic acid sequences.
Lato
S M
SM
Department of Chemistry, Indiana University, Bloomington 47405, USA.
Boles
A R
AR
Ellington
A D
AD
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D002473:Cell Wall / Q000737:chemistry / Q000378:metabolism; D002846:Chromatography, Affinity; D019143:Evolution, Molecular; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism; D037102:Lectins; D008024:Ligands; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry; D012313:RNA / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D016337:RNA, Catalytic / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D006023:Glycoproteins; D037102:Lectins; D008024:Ligands; D009844:Oligosaccharides; D016337:RNA, Catalytic; D012313:RNA