Antibiotic inhibition of group I ribozyme function

Area of Science:

• Biochemistry
• Molecular Biology
• Evolutionary Biology

Background:

• The RNA world hypothesis posits that RNA preceded DNA and proteins, serving as both genetic material and catalyst.
• Ancient catalytic RNAs may have had their functions modulated by small molecules, potentially including early forms of antibiotics.
• The ribosome, a complex RNA-protein machine, is central to protein synthesis and may hold clues to RNA-antibiotic coevolution.

Purpose of the Study:

• To investigate the interaction between aminoglycoside antibiotics and catalytic RNA.
• To determine if aminoglycoside antibiotics affect RNA splicing, particularly group I introns.
• To explore the potential coevolutionary relationship between antibiotics, RNA, and early biological systems.

Main Methods:

• Tested the effect of aminoglycoside antibiotics on the second step of splicing of the T4 phage-derived td intron.
• Examined the impact of these antibiotics on the splicing of other group I and group II introns.
• Compared the binding affinity and specificity of antibiotics to group I introns and ribosomal RNA (rRNA).

Main Results:

• A set of aminoglycoside antibiotics was found to inhibit the second step of splicing of the T4 phage-derived td intron.
• Splicing of other group I introns was also inhibited, while group II intron splicing was not affected.
• The antibiotics demonstrated similar affinity and specificity for group I introns and ribosomal RNAs.

Conclusions:

• Catalytic RNA interacts not only with nucleotides and amino acids but also with sugars, as evidenced by antibiotic interactions.
• The observed inhibition suggests a potential coevolutionary link between aminoglycoside antibiotics, group I introns, and ribosomal RNA.
• Conserved structures in group I introns and rRNAs likely mediate the recognition by these antibiotics, supporting evolutionary connections.