Allosteric ribozymes sensitive to the second messengers cAMP and cGMP

Koizumi, Makoto; Kerr, Jo Nita Q.; Soukup, Garrett A.; Breaker, Ronald R.

doi:10.1093/nass/42.1.275

Cited by 64 publications

(80 citation statements)

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“…In hemoglobin, the T (unbound)-to-R (bound) transition occurs when one O 2 molecule binds to the heme group, causing a conformational change that displaces the F helix, inducing a shift of the intersubunit contacts that stabilize the high-affinity O 2 state (Turner et al 1992;Royer et al 2001). The binding of a ligand at one site that causes subsequent conformational changes that affect ligand binding at another site is a fundamental mechanism inclusive of other allosteric proteins (Copeland, 2000) and in the design of allosteric ribozymes (Koizumi et al 1999;Jose et al 2001). Our data provide a partial view of the interactions between the aptamers that facilitate cooperativity in this novel RNA system.…”

Section: A Mechanism For Cooperative Glycine Bindingmentioning

confidence: 99%

Identification of a tertiary interaction important for cooperative ligand binding by the glycine riboswitch

Erion¹,

Strobel²

2010

RNA

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The glycine riboswitch has a tandem dual aptamer configuration, where each aptamer is a separate ligand-binding domain, but the aptamers function together to bind glycine cooperatively. We sought to understand the molecular basis of glycine riboswitch cooperativity by comparing sites of tertiary contacts in a series of cooperative and noncooperative glycine riboswitch mutants using hydroxyl radical footprinting, in-line probing, and native gel-shift studies. The results illustrate the importance of a direct or indirect interaction between the P3b hairpin of aptamer 2 and the P1 helix of aptamer 1 in cooperative glycine binding. Furthermore, our data support a model in which glycine binding is sequential; where the binding of glycine to the second aptamer allows tertiary interactions to be made that facilitate binding of a second glycine molecule to the first aptamer. These results provide insight into cooperative ligand binding in RNA macromolecules.

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Section: A Mechanism For Cooperative Glycine Bindingmentioning

confidence: 99%

Identification of a tertiary interaction important for cooperative ligand binding by the glycine riboswitch

Erion¹,

Strobel²

2010

RNA

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“…Although no allosterically regulated ribozymes have yet been identified in nature (but see the section below on oligonucleotide-regulated ribozymes), many have been developed artificially. This has been accomplished by the often complementary approaches of rational design (Tang andBreaker 1997, 1998;Kuwabara et al 1998;Vaish et al 2002;Wang and Sen 2002) and in vitro selection (Koizumi et al 1999;Robertson and Ellington 1999;Soukup and Breaker 1999b). Allosteric regulation has been imposed onto the hammerhead (Kertsburg and Soukup 2002), HDV (Kertsburg and Soukup 2002), hairpin , Tetrahymena group I intron (Kertsburg and Soukup 2002), and X-motif ribozymes (Kertsburg and Soukup 2002).…”

Section: Allosteric Ribozyme Sensors (Aptazymes) and General "Communimentioning

confidence: 99%

“…Allosteric regulation has been imposed onto the hammerhead (Kertsburg and Soukup 2002), HDV (Kertsburg and Soukup 2002), hairpin , Tetrahymena group I intron (Kertsburg and Soukup 2002), and X-motif ribozymes (Kertsburg and Soukup 2002). The activity-modulating ligands include ATP (Tang and Breaker 1997;Robertson and Ellington 2000), theophylline (Soukup and Breaker 1999a;Robertson and Ellington 2000;Soukup et al 2000), flavin mononucleotide (FMN; Araki et al 1998Araki et al , 2001Breaker 1999a, 1999b;Robertson and Ellington 2000), cyclic nucleotide monophosphates (cNMPs; Koizumi et al 1999), doxycycline (Piganeau et al 2000), 3-methylxanthine (Soukup et al 2000), and pefloxacin (Piganeau et al 2001), as well as various metal ions (Seetharaman et al 2001), oligonucleotides (Porta and Lizardi 1995;Kuwabara et al 1998;Robertson and Ellington 1999;Komatsu et al 2000), and several proteins Vaish et al 2002). Allosteric regulation has also been extended to DNA enzymes that are activated by ATP (Levy and Ellington 2002).…”

Section: Allosteric Ribozyme Sensors (Aptazymes) and General "Communimentioning

confidence: 99%

“…The activity enhancement upon ligand activation of an aptazyme is typically between 10 and 10 3 ; the higher end of this range is more than sufficient for practical biosensor assays. In the most favorable case yet reported, that of a ribozyme obtained by Breaker and coworkers that is allosterically upregulated by cGMP, the enhancement is 5000-fold (Koizumi et al 1999). The mechanism by which ligand binding is coupled to ribozyme activation is usually not known in detail, but this is generally thought to involve structural stabilization of the catalytically active ribozyme conformation upon ligand binding (Soukup and Breaker 1999a).…”

Section: Allosteric Ribozyme Sensors (Aptazymes) and General "Communimentioning

confidence: 99%

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Rube Goldberg goes (ribo)nuclear? Molecular switches and sensors made from RNA

Silverman¹

2003

RNA

110

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Switches and sensors play important roles in our everyday lives. The chemical properties of RNA make it amenable for use as a switch or sensor, both artificially and in nature. This review focuses on recent advances in artificial RNA switches and sensors. Researchers have been applying classical biochemical principles such as allostery in elegant ways that are influencing the development of biosensors and other applications. Particular attention is given here to allosteric ribozymes (aptazymes) that are regulated by small organic molecules, by proteins, or by oligonucleotides. Also discussed are ribozymes whose activities are controlled by various nonallosteric strategies.

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“…These latter artificial regulators are called allosteric ribozymes, or aptazymes. To date, several aptazymes have been constructed using hammerhead ribozyme for various types of ligands, including ATP (Tang and Breaker 1997), FMN (Araki et al 1998;Soukup and Breaker 1999a), theophylline (Soukup and Breaker 1999a;Wieland and Hartig 2008), cyclic nucleotide monophosphates (Koizumi et al 1999), and thiamine pyrophosphate (TPP) (Wieland et al 2009). These aptazymes have been used for a wide range of applications, such as 5 artificial gene regulation in vivo (Kumar et al 2009;Carothers et al 2011) and as biosensors in vitro (Breaker 2002;Hesselberth et al 2003;Ogawa and Maeda 2007).…”

Section: Introductionmentioning

confidence: 99%

Kinetic analysis of aptazyme-regulated gene expression in a cell-free translation system: Modeling of ligand-dependent and -independent expression

Kobori

Ichihashi²,

Kazuta³

et al. 2012

RNA

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Aptazymes are useful as RNA-based switches of gene expression responsive to several types of compounds. One of the most important properties of the switching ability is the signal/noise (S/N) ratio, i.e., the ratio of gene expression in the presence of ligand to that in the absence of ligand. The present study was performed to gain a quantitative understanding of how the aptazyme S/N ratio is determined by factors involved in gene expression, such as transcription, RNA self-cleavage, RNA degradation, protein translation, and their ligand dependencies. We performed switching of gene expression using two onswitch aptazymes with different properties in a cell-free translation system, and constructed a kinetic model that quantitatively describes the dynamics of RNA and protein species involved in switching. Both theoretical and experimental analyses consistently demonstrated that factors determining both the absolute value and the dynamics of the S/N ratio are highly dependent on the routes of translation in the absence of ligand: translation from the ligand-independently cleaved RNA or leaky translation from the noncleaved RNA. The model obtained here is useful to assess the factors that restrict the S/N ratio and to improve aptazymes more efficiently.

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Allosteric ribozymes sensitive to the second messengers cAMP and cGMP

Cited by 64 publications

References 0 publications

Identification of a tertiary interaction important for cooperative ligand binding by the glycine riboswitch

Identification of a tertiary interaction important for cooperative ligand binding by the glycine riboswitch

Rube Goldberg goes (ribo)nuclear? Molecular switches and sensors made from RNA

Kinetic analysis of aptazyme-regulated gene expression in a cell-free translation system: Modeling of ligand-dependent and -independent expression

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