Orthogonal Riboswitches for Tuneable Coexpression in Bacteria

Dixon, Neil; Robinson, Christopher J.; Geerlings, Torsten H.; Duncan, John N.; Drummond, Sheona P; Micklefield, Jason

doi:10.1002/anie.201109106

Cited by 49 publications

(44 citation statements)

References 30 publications

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“…Some riboswitches control vital metabolic and virulence genes in pathogenic species, and the identification of novel riboswitch-specific antibiotic scaffolds presents an attractive strategy for therapeutic intervention. Additionally, riboswitches are potential targets for the construction of artificial genetic circuits that could be controlled by nonnatural compounds (Dixon et al, 2012). Understanding the regulatory and structural principles exploited by natural riboswitches will help in the development of synthetic riboswitches that respond to a particular ligand (Suess et al, 2004; Verhounig et al, 2010) and the useful reprogramming of bacteria, for instance, to seek and destroy an unwanted herbicide (Sinha et al, 2010).…”

Section: Future Challenges and Perspectivesmentioning

confidence: 99%

A Decade of Riboswitches

Serganov

Nudler

2013

Cell

869

772

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Riboswitches were discovered in 2002 in bacteria as RNA-based intracellular sensors of vitamin derivatives. During the last decade, naturally occurring RNA sensor elements have been found to bind a range of small metabolites and ions and to exert regulatory control of transcription, translation, splicing, and RNA stability. Extensive biochemical, structural, and genetic studies have established the basic principles underpinning riboswitch function in all three kingdoms of life with implications for developing antibiotics, designing new molecular sensors, and integrating riboswitches into synthetic circuits.

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Section: Future Challenges and Perspectivesmentioning

confidence: 99%

A Decade of Riboswitches

Serganov

Nudler

2013

Cell

869

772

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“…To demonstrate how orthogonal riboswitches can assist in the regulatory control of multiple genes, the authors created dual and single promoter operons in which the natural add and the M6 translational “ON” riboswitches regulate the DSRed and eGFP genes, respectively [126]. In both examples, each gene was specifically induced by its cognate effector (2-aminopurine for add and ammeline for M6).…”

Section: Application Of Purine Riboswitchesmentioning

confidence: 99%

“…A more useful modular switch is one that can induce gene expression in response to ligand binding, like the M6 riboswitch [125, 126]. However, most of the “ON” switches surveyed for potential modularity have significant sequence overlap between the two domains, preventing their simple decoupling at a defined boundary like the metE riboswitch [130].…”

Section: Application Of Purine Riboswitchesmentioning

confidence: 99%

The purine riboswitch as a model system for exploring RNA biology and chemistry

Porter¹,

Marcano-Velázquez²,

Batey³

2014

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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Over the past decade the purine riboswitch, and in particular its nucleobase-binding aptamer domain, has emerged as an important model system for exploring various aspects of RNA structure and function. Its relatively small size, structural simplicity and readily observable activity enable application of a wide variety of experimental approaches towards the study of this RNA. These analyses have yielded important insights into small molecule recognition, co-transcriptional folding and secondary structural switching, and conformational dynamics that serve as a paradigm for other RNAs. In this article, the current state of understanding of the purine riboswitch family is examined and how this growing knowledge base is starting to be exploited in the creation of novel RNA devices.

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“…Thus, substituting the original ORF with a new one on a ‘start codon for start codon’ basis can nullify the desired riboswitch response to a given ligand 17 . To overcome this lack of modularity, many studies have created fusions comprised of a riboswitch, the first few hundred base pairs of its working ORF, and a gene of interest 18–21 . However, this approach fails in many circumstances as it can alter the gene’s functionality, since many enzymes, such as the endoribonuclease XendoU, will not work with the inclusion of large 5′ fusions 22–27 .…”

Section: Introductionmentioning

confidence: 99%

Ribo-attenuators: novel elements for reliable and modular riboswitch engineering

Folliard

Mertins

Steel

et al. 2017

Sci Rep

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Riboswitches are structural genetic regulatory elements that directly couple the sensing of small molecules to gene expression. They have considerable potential for applications throughout synthetic biology and bio-manufacturing as they are able to sense a wide range of small molecules and regulate gene expression in response. Despite over a decade of research they have yet to reach this considerable potential as they cannot yet be treated as modular components. This is due to several limitations including sensitivity to changes in genetic context, low tunability, and variability in performance. To overcome the associated difficulties with riboswitches, we have designed and introduced a novel genetic element called a ribo-attenuator in Bacteria. This genetic element allows for predictable tuning, insulation from contextual changes, and a reduction in expression variation. Ribo-attenuators allow riboswitches to be treated as truly modular and tunable components, thus increasing their reliability for a wide range of applications.

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Orthogonal Riboswitches for Tuneable Coexpression in Bacteria

Cited by 49 publications

References 30 publications

A Decade of Riboswitches

A Decade of Riboswitches

The purine riboswitch as a model system for exploring RNA biology and chemistry

Ribo-attenuators: novel elements for reliable and modular riboswitch engineering

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