Why do riboswitches make good drug targets for antibiotic development?
Why do riboswitches make good drug targets for antibiotic development?
Riboswitches are exciting targets for novel antibiotics and chemical tools due to their structural sophistication, specificity, and their function as genetic regulators of essential bacterial genes.
What is Riboswitch and how is it work?
The riboswitch is a part of an mRNA molecule that can bind and target small target molecules. An mRNA molecule may contain a riboswitch that directly regulates its own expression. The riboswitch displays the ability to regulate RNA by responding to concentrations of its target molecule.
Are riboswitches common in bacteria?
Most known riboswitches occur in bacteria, but functional riboswitches of one type (the TPP riboswitch) have been discovered in archaea, plants and certain fungi. TPP riboswitches have also been predicted in archaea, but have not been experimentally tested.
How do translational riboswitches and transcriptional riboswitches differ?
How do translational riboswitches and transcriptional riboswitches differ? Translational riboswitches are mainly observed in Gram-negative bacteria while transcriptional riboswitches are associated with Gram-positive bacteria.
What do riboswitches demonstrate?
Riboswitches demonstrate that naturally occurring RNA can bind small molecules specifically, a capability that many previously believed was the domain of proteins or artificially constructed RNAs called aptamers.
Are riboswitches specific to prokaryotes?
Riboswitches are now seen as a major prokaryotic gene regulation mechanism, for example they control ~4% of the genes in Bacillus subtilis. Studies on the NMT1 gene which is a gene involved in TPP metabolism, and known to be repressed by excess thiamine, showed that thiamine caused alternative splicing of this gene.
What is the function of cyclic dimeric GMP in bacterial global regulation systems?
Cyclic di-GMP has been shown to regulate biofilm formation, motility, virulence, the cell cycle, differentiation, and other processes. Most c-di-GMP-dependent signaling pathways control the ability of bacteria to interact with abiotic surfaces or with other bacterial and eukaryotic cells.
What are the mechanisms by which riboswitches regulate translation and transcription?
Currently, some of the most common mechanisms for riboswitch-mediated gene control involve the direct regulation of translation initiation, or the inhibition of protein production more indirectly by altering mRNA stability or by changing the primary sequence of mRNAs via alternative splicing.
How do translational Riboswitches and transcriptional Riboswitches differ?
How are Regulons regulated?
In molecular genetics, a regulon is a group of genes that are regulated as a unit, generally controlled by the same regulatory gene that expresses a protein acting as a repressor or activator. The term stimulon is sometimes used to refer to the set of genes whose expression responds to specific environmental stimuli.
What’s the difference between operon and regulon?
Operon is a functional DNA unit in prokaryotes that consists of several genes that are regulated by a single promoter and an operator. Regulon is a functional genetic unit that is composed of a noncontiguous group of genes that are regulated by a single regulatory molecule.
Do all bacteria use quorum sensing?
Both Gram-positive and gram-negative bacteria use quorum sensing, but there are some major differences in their mechanisms.
How are riboswitches different from other RNA drug targets?
Riboswitches are fundamentally different RNA drug targets, in that they have evolved as structured receptors for the purpose of binding low-molecular weight ligands. As a consequence, riboswitches form ligand-receptor interfaces with a level of structural complexity and selectivity that approaches that of proteins.
How are riboswitches used to regulate gene expression in bacteria?
This need could potentially be filled by riboswitches—messenger RNA (mRNA) structures that regulate gene expression in bacteria. Riboswitches are unique among RNAs that serve as drug targets in that they have evolved to form structured and highly selective receptors for small drug-like metabolites.
Are there any drugs that target ribosomal RNA?
Many currently marketed antibacterial drugs, including the two most recently approved 17, target ribosomal RNA (rRNA) structures 18, 19. Numerous other RNA motifs also have been explored as potential drug targets 20.