China
Africa
Explore chapters and articles related to this topic
The Emerging Field of RNA Nanotechnology
Published in Lajos P. Balogh, Nano-Enabled Medical Applications, 2020
Riboswitches [102] are RNA components that bind small molecules and control gene expression in response to an organism’s needs. As a biological control mechanism, riboswitches can recognize metabolites, induce premature termination of mRNA transcription, block ribosomes from translating mRNAs, cleave mRNAs, and even trigger mRNA destruction. Therefore, RNA switches can be reengineered to create a new generation of controllers regulated by drug-like molecules to tune the expression levels of targeted genes in vivo. Such RNA-based gene-control machines hold promise in future gene therapies by supplying nanoscale c/s-acting modulation [103, 104].
Beyond Enzyme Kinetics
Published in Clive R. Bagshaw, Biomolecular Kinetics, 2017
In addition to the well-known helical duplex structures, nucleic acids and RNA, in particular, can form higher-order (tertiary) structures. The kinetics of formation of such states is analogous to protein folding (Section 5.1), with kinetics that may appear relatively simple, but encompass a large number of microstates [218,219]. Some RNA molecules, known as riboswitches, change conformation on binding small metabolites and constitute important cellular control mechanisms [205,220–222]. In addition, some RNA molecules show catalytic activity, a finding that overturned the idea that all enzymes were proteins [223]. However, such ribozymes catalyze a limited repertoire of reactions (typically cleavage of the ribophosphate backbone of a nucleic acid). Often they only undergo a single turnover and hence are not catalysts in the conventional sense [224]. Furthermore, reaction times are on the order of minutes rather than milliseconds typical of proteinaceous enzymes [225]. This characteristic allows transient kinetic reactions to be followed by manual quenching and analysis by gel electrophoresis [224].
Riboswitches as therapeutic targets: promise of a new era of antibiotics
Published in Expert Opinion on Therapeutic Targets, 2023
Emily Ellinger, Adrien Chauvier, Rosa A. Romero, Yichen Liu, Sujay Ray, Nils G. Walter
Riboswitches are structured non-coding RNA elements commonly embedded in the 5’ UTRs of mRNA that regulate downstream genes in response to the binding of small molecules or ions. They are important for efficient resource allocation during times of stress and changing environmental conditions [26]. Riboswitches consist of two domains, an aptamer domain that binds a ligand(s) and an expression platform involved in the regulation of gene expression. The binding of a ligand to the aptamer domain triggers a conformational change within the expression platform (which are often overlapping) that either terminates or promotes the expression of downstream genes [11,27,28] (Figure 2). Currently, 55 classes of riboswitches are known, distinguished by the specific ligand they bind, with many more ‘boutique’ classes expected to be found in individual bacterial strains adapted to unique environmental niches [29]. Riboswitches are further stratified based on their mechanism of regulation; most control gene expression at the level of transcription or translation (Figure 2), which can eventually lead to RNA degradation [11,12,27]. Intriguingly, transcriptional riboswitches are found primarily in Gram-positive bacteria. In contrast, translational riboswitches are confined mainly to Gram-negative bacteria that also contain the conserved Rho protein, which serves as a transcription terminator. Translational riboswitches have been found to trigger Rho-dependent transcription termination thus regulating both transcription and translation in Gram-negative bacteria [30].
Genome-wide bioinformatics analysis of FMN, SAM-I, glmS, TPP, lysine, purine, cobalamin, and SAH riboswitches for their applications as allosteric antibacterial drug targets in human pathogenic bacteria
Published in Expert Opinion on Therapeutic Targets, 2019
Nikolet Pavlova, Robert Penchovsky
To overrule the growing number of AR, we have to pare down the use of antibiotics. In this way, we will decline the new unknown resistant bacteria. Likewise, we have to enlarge the antibacterial vaccination programs. The development of new antibiotics that can deal with multidrug-resistant bacterial pathogens is urgent. In general, various types of RNA are proven to be suitable as antibacterial drug targets. In many currently marketed antibacterial drugs, the ligand binding to the targeted RNA is a fortuitous interaction rather than a selective function of these RNAs [11]. Riboswitches are very different drug targets evolving as molecular sensors for binding small molecules in the cell. Interestingly, riboswitches in Gram-negative bacteria prefer regulation of translation initiation, whereas Gram-positive bacteria favor transcription termination, a correlation that probably reflects the higher frequency of polycistronic genes in Gram-positive bacteria.
Strategies for targeting RNA with small molecule drugs
Published in Expert Opinion on Drug Discovery, 2023
Christopher L. Haga, Donald G. Phinney
Riboswitches are naturally occurring RNA aptamers that bind specific small molecules to regulate gene expression, most often in bacteria [39]. These structured RNA sequences are usually found in the untranslated region of mRNA and consist of an evolutionarily conserved ligand-binding aptamer domain working in conjunction with a variable sequence expression platform domain that serves to regulate downstream expression. Upon binding to a cognate ligand, conformation changes occur within the RNA, inducing or inhibiting gene expression, through several mechanisms such as transcription and translation termination, transcription antitermination, translational activation, and alternative splicing.