Adenine-Aptamer Complexes

Meli, Marc; Vergne, Jacques; Décout, Jean‐Luc; Maurel, Marie‐Christine

doi:10.1074/jbc.m107130200

Cited by 42 publications

(12 citation statements)

References 32 publications

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“…10 mm, but bind adenosine much more weakly (K d ca. 500 mm ; [67]). Aptamers selected to bind cAMP [68] or to the triphosphate of ATP [69] also have sequence and structural motifs that differ from those of the anti-ATP aptamer.…”

mentioning

confidence: 97%

Ribozyme Catalysis of Metabolism in the RNA World

Chen¹,

Li²,

Ellington³

2007

Chemistry & Biodiversity

172

105

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In vitro selection has proven to be a useful means of explore the molecules and catalysts that may have existed in a primordial 'RNA world'. By selecting binding species (aptamers) and catalysts (ribozymes) from random sequence pools, the relationship between biopolymer complexity and function can be better understood, and potential evolutionary transitions between functional molecules can be charted. In this review, we have focused on several critical events or transitions in the putative RNA world: RNA self-replication; the synthesis and utilization of nucleotide-based cofactors; acyl-transfer reactions leading to peptide and protein synthesis; and the basic metabolic pathways that are found in modern living systems.

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mentioning

confidence: 97%

Ribozyme Catalysis of Metabolism in the RNA World

Chen¹,

Li²,

Ellington³

2007

Chemistry & Biodiversity

172

105

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“…We recently reported the isolation of new RNA aptamers able to bind adenine in a novel mode of purine recognition (18). Adenine is a likely prebiotic analog of histidine.…”

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confidence: 99%

In Vitro Selection of Adenine-dependent Hairpin Ribozymes

Meli

Vergne

Maurel

2003

Journal of Biological Chemistry

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Adenine-dependent hairpin ribozymes were isolated by in vitro selection from a degenerated hairpin ribozyme population. Two new adenine-dependent ribozymes catalyze their own reversible cleavage in the presence of free adenine. Both aptamers have Mg 2؉ requirements for adenine-assisted cleavage similar to the wild-type hairpin ribozyme. Cleavage kinetics studies in the presence of various other small molecules were compared. The data suggest that adenine does not induce RNA self-cleavage in the same manner for both aptamers. In addition, investigations of pH effects on catalytic rates show that both adenine-dependent aptamers are more active in basic conditions, suggesting that they use new acid/base catalytic strategies in which adenine could be involved directly. The discovery of hairpin ribozymes dependent on adenine for their reversible selfcleavage presents considerable biochemical and evolutionary interests because we show that RNA is able to use exogenous reactive molecules to enhance its own catalytic activity. Such a mechanism may have been a means by which the ribozymes of the RNA world enlarged their chemical repertoire.The RNA world theory assumes that modern life arose from molecular ancestors in which RNA molecules both stored genetic information and catalyzed chemical reactions (1-4). According to this scenario, ribozymes of the RNA world would have been able to self-replicate (5) and to control complex metabolisms with an expanded chemical repertoire (6, 7). Until recently, RNA catalysis was believed to be restricted to phosphate chemistry, but in vitro selection experiments and recent discoveries concerning natural ribozymes have demonstrated that the catalytic capacities of RNA are far more promising and exciting than previously anticipated (8 -13). However, in comparison with proteins, the chemical spectrum of ribozymes remains limited because of the limited chemical diversity of RNA, which is composed of only four different building blocks.Yet RNA could increase its range of functionalities by incorporating catalytic building blocks such as imidazole, thiol, and functional amino and carboxylate groups (14, 15). Moreover, primeval nucleotides were not necessarily restricted to standard nucleotides; modified nucleotides may have played a role in catalysis in the RNA world (16,17).Another way for RNA to increase its chemical diversity would consist in the binding of exogenous molecules carrying reactive groups and handling them as catalytic cofactors. We recently reported the isolation of new RNA aptamers able to bind adenine in a novel mode of purine recognition (18). Adenine is a likely prebiotic analog of histidine. Its catalytic capabilities are equivalent to histidine because of the presence of a free imidazole moiety (19 -21). It was previously shown that when adenine is placed in a favorable microenvironment, its catalytic efficiency is strongly enhanced (22-24). Such favorable microenvironments could result from adenine binding to RNA and thereby providing catalytic sites. In this perspe...

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“…After identifying several aptamer sequences capable of binding adenine, the highest affinity aptamers were assayed with molecules structurally similar to adenine. Interestingly, 6-MAP (6-methylaminopurine) bound with higher affinity than adenine itself [29], perhaps reflecting the N 6 -linked adenine configuration used in the SELEX screen. 6-MAP has a methyl group at position N 6 similar to both the SELEX matrix used for aptamer selection and to naturally occurring cytokinins (Figure 1).…”

Section: Presentation Of the Hyposthesismentioning

confidence: 99%

Riboswitches as hormone receptors: hypothetical cytokinin-binding riboswitches in Arabidopsis thaliana

Grojean

Downes

2010

Biology Direct

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BackgroundRiboswitches are mRNA elements that change conformation when bound to small molecules. They are known to be key regulators of biosynthetic pathways in both prokaryotes and eukaryotes.Presentation of the HypothesisThe hypothesis presented here is that riboswitches function as receptors in hormone perception. We propose that riboswitches initiate or integrate signaling cascades upon binding to classic signaling molecules. The molecular interactions for ligand binding and gene expression control would be the same as for biosynthetic pathways, but the context and the cadre of ligands to consider is dramatically different. The hypothesis arose from the observation that a compound used to identify adenine binding RNA sequences is chemically similar to the classic plant hormone, or growth regulator, cytokinin. A general tenet of the hypothesis is that riboswitch-binding metabolites can be used to make predictions about chemically related signaling molecules. In fact, all cell permeable signaling compounds can be considered as potential riboswitch ligands. The hypothesis is plausible, as demonstrated by a cursory review of the transcriptome and genome of the model plant Arabidopsis thaliana for transcripts that i) contain an adenine aptamer motif, and ii) are also predicted to be cytokinin-regulated. Here, one gene, CRK10 (for Cysteine-rich Receptor-like Kinase 10, At4g23180), contains an adenine aptamer-related sequence and is down-regulated by cytokinin approximately three-fold in public gene expression data. To illustrate the hypothesis, implications of cytokinin-binding to the CRK10 mRNA are discussed.Testing the hypothesisAt the broadest level, screening various cell permeable signaling molecules against random RNA libraries and comparing hits to sequence and gene expression data bases could determine how broadly the hypothesis applies. Specific cases, such as CRK10 presented here, will require experimental validation of direct ligand binding, altered RNA conformation, and effect on gene expression. Each case will be different depending on the signaling pathway and the physiology involved.Implications of the hypothesisThis would be a very direct signal perception mechanism for regulating gene expression; rivaling animal steroid hormone receptors, which are frequently ligand dependent transcription initiation factors. Riboswitch-regulated responses could occur by modulating target RNA stability, translatability, and alternative splicing - all known expression platforms used in riboswitches. The specific illustration presented, CRK10, implies a new mechanism for the perception of cytokinin, a classic plant hormone. Experimental support for the hypothesis would add breadth to the growing list of important functions attributed to riboswitches.ReviewersThis article was reviewed by Anthony Poole, Rob Knight, Mikhail Gelfand.

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Adenine-Aptamer Complexes

Cited by 42 publications

References 32 publications

Ribozyme Catalysis of Metabolism in the RNA World

Ribozyme Catalysis of Metabolism in the RNA World

In Vitro Selection of Adenine-dependent Hairpin Ribozymes

Riboswitches as hormone receptors: hypothetical cytokinin-binding riboswitches in Arabidopsis thaliana

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