Modular arrangement of regulatory RNA elements

Roßmanith, Johanna; Narberhaus, Franz

doi:10.1080/15476286.2016.1274853

Cited by 12 publications

(6 citation statements)

References 47 publications

(47 reference statements)

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“…Those aptamers in combination with different expression platforms have also presented high variability. Except for the utilization of naturally occurring riboswitches, the in vitro systematic evolution of ligands by exponential enrichment (SELEX) is also used for the identification of aptamers that bind non-natural ligands [ 165 ]. However, the conformational changes that are required to make the aptamer active after ligand binding and the artificial conditions under which the aptamers are selected may hamper their functionality in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…By overcoming these barriers, engineered riboswitches managed to halt translation both in a cap- and IRES-dependent manner, as well as by controlling ribosomal shunting and splicing. Further research has also shown that gene expression can be regulated from synthetic riboswitches through RNA self-cleavage, by interfering with the RNAi pathway or by controlling microRNA (miRNA) production [ 164 , 165 , 166 , 167 ].…”

Section: Discussionmentioning

confidence: 99%

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A Riboswitch-Driven Era of New Antibacterials

et al. 2022

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Riboswitches are structured non-coding RNAs found in the 5′ UTR of important genes for bacterial metabolism, virulence and survival. Upon the binding of specific ligands that can vary from simple ions to complex molecules such as nucleotides and tRNAs, riboswitches change their local and global mRNA conformations to affect downstream transcription or translation. Due to their dynamic nature and central regulatory role in bacterial metabolism, riboswitches have been exploited as novel RNA-based targets for the development of new generation antibacterials that can overcome drug-resistance problems. During recent years, several important riboswitch structures from many bacterial representatives, including several prominent human pathogens, have shown that riboswitches are ideal RNA targets for new compounds that can interfere with their structure and function, exhibiting much reduced resistance over time. Most interestingly, mainstream antibiotics that target the ribosome have been shown to effectively modulate the regulatory behavior and capacity of several riboswitches, both in vivo and in vitro, emphasizing the need for more in-depth studies and biological evaluation of new antibiotics. Herein, we summarize the currently known compounds that target several main riboswitches and discuss the role of mainstream antibiotics as modulators of T-box riboswitches, in the dawn of an era of novel inhibitors that target important bacterial regulatory RNAs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A Riboswitch-Driven Era of New Antibacterials

et al. 2022

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“…Since several color variations of light-up RNA aptamers have been reported recently, construction of signaling aptamers, which emit fluorescence at different wavelengths in response to different input target molecules, would enable simultaneous imaging of multiple molecules at the single-cell level. The strategy is applicable for not only optimizing signaling aptamers but also for constructing RNAs with modular function as rational design of their allosterically regulated functions is challenging . In addition, the basic technology used for constructing R-CAMPs is that used for next generation sequencing.…”

Section: Discussionmentioning

confidence: 99%

Signaling Aptamer Optimization through Selection Using RNA-Capturing Microsphere Particles

Endoh

Sugimoto

2020

Anal. Chem.

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An RNA signaling aptamer is composed of two units: a sensing aptamer that binds the input target molecule and a working aptamer that binds the output target molecule to result in a detectable signal. A conformational change of the signaling aptamer that induces an allosteric interaction with the output target molecule in response to the input target molecule depends on a junction region, which connects the two aptamer units. Efficient and effective optimization of the junction region remains a technical challenge. In this study, we demonstrate a simple strategy for optimizing the junction region through functional RNA selection using RNA-capturing microsphere particles. From approximately 0.2 million sequence variants, a signaling aptamer that enabled intracellular detection of S-adenosyl methionine with a high signal-to-noise ratio, which is approximately 2-fold higher relative fluorescence increment compared to the previously reported signaling aptamer, was obtained after single round of selection. The technology demonstrated here can be used to select RNA sequences that carry out specific functions in response to particular stimuli.

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“…Modularity is an essential concept in engineering fields that can be applied to synthetic biology. However, engineered devices may not actually exhibit modular behaviour and often a device's features may change under different conditions (30,39,40). Designing the TSD, we observed an influence of the environment surrounding the aptamer cis -elements on its switching behaviour.…”

Section: Discussionmentioning

confidence: 99%

Robust gene expression control in human cells with a novel universal TetR aptamer splicing module

Mol

Groher

Schreiber

et al. 2019

Nucleic Acids Research

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Fine-tuning of gene expression is desirable for a wide range of applications in synthetic biology. In this context, RNA regulatory devices provide a powerful and highly functional tool. We developed a versatile, robust and reversible device to control gene expression by splicing regulation in human cells using an aptamer that is recognized by the Tet repressor TetR. Upon insertion in proximity to the 5′ splice site, intron retention can be controlled via the binding of TetR to the aptamer. Although we were able to demonstrate regulation for different introns, the genomic context had a major impact on regulation. In consequence, we advanced the aptamer to develop a splice device. Our novel device contains the aptamer integrated into a context of exonic and intronic sequences that create and maintain an environment allowing a reliable and robust splicing event. The exon-born, additional amino acids will then be cleaved off by a self-cleaving peptide. This design allows portability of the splicing device, which we confirmed by demonstrating its functionality in different gene contexts. Intriguingly, our splicing device shows a high dynamic range and low basal activity, i.e. desirable features that often prove a major challenge when implementing synthetic biology in mammalian cell lines.

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Modular arrangement of regulatory RNA elements

Cited by 12 publications

References 47 publications

A Riboswitch-Driven Era of New Antibacterials

A Riboswitch-Driven Era of New Antibacterials

Signaling Aptamer Optimization through Selection Using RNA-Capturing Microsphere Particles

Robust gene expression control in human cells with a novel universal TetR aptamer splicing module

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