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Published on: September 21, 2017
Aminoglycoside interactions with RNAs and nucleases
L A Kirsebom1, A Virtanen, N E Mikkelsen
1Department of Cell and Molecular Biology, Biomedical Center, Uppsala University, Box 596, Uppsala, Sweden. Leif.Kirsebom@icm.uu.se
Handbook of Experimental Pharmacology
|April 6, 2006
Summary
Aminoglycosides are crucial for developing new antibiotics by targeting noncoding RNAs. Understanding their interaction with RNA, including ribosomal RNAs (rRNAs), is key to combating antibiotic resistance.
Area of Science:
- Pharmacology and Molecular Biology
- Antimicrobial Resistance Research
- RNA Therapeutics
Background:
- The rise of multiresistant bacterial strains necessitates novel antibiotic development.
- Aminoglycosides are known to interact with noncoding RNAs, particularly ribosomal RNAs (rRNAs), and proteins like ribonucleases.
- Understanding these interactions is vital for antibiotic discovery.
Purpose of the Study:
- To review the current understanding of aminoglycoside-RNA interactions.
- To discuss mechanisms of aminoglycoside inactivation.
- To highlight noncoding RNAs as potential targets for next-generation antibiotics.
Main Methods:
- Literature review of studies on aminoglycoside-RNA interactions.
- Analysis of mechanisms contributing to aminoglycoside resistance.
- Exploration of non-rRNA noncoding RNAs as therapeutic targets.
Main Results:
- Aminoglycosides interfere with the function of various noncoding RNAs, with rRNAs being extensively studied.
- Mechanisms of aminoglycoside inactivation are a significant concern due to evolving bacterial resistance.
- Non-rRNA noncoding RNAs represent promising, yet underexplored, targets for novel antibiotics.
Conclusions:
- Knowledge of aminoglycoside-RNA interactions is fundamental for developing new antibiotic classes.
- Exploring interactions with both known and novel noncoding RNAs can lead to effective antimicrobial strategies.
- Targeting RNA offers a promising avenue to overcome current antibiotic resistance challenges.
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01:23Types of RNA
Overview
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
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01:23RNA Interference
RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
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