The potential versatility of <scp>RNA</scp> catalysis

Wilson, Timothy J.; Lilley, David M.J.

doi:10.1002/wrna.1651

Cited by 24 publications

(25 citation statements)

References 79 publications

(108 reference statements)

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“…Intriguingly, the α-site primary amine is solvent accessible (Supplementary Fig. 7 ), providing a key functional group absent from the RNA chemical repertoire 47 ; in contrast, the β-preQ 1 WC face is solvent accessible. Notably, O6-methyl preQ 1 shows site-specific preQ 1 -I II riboswitch methylation 48 , providing a precedent for ligand-mediated chemical transformation of RNA.…”

Section: Discussionmentioning

confidence: 99%

A small RNA that cooperatively senses two stacked metabolites in one pocket for gene control

et al. 2022

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Riboswitches are structured non-coding RNAs often located upstream of essential genes in bacterial messenger RNAs. Such RNAs regulate expression of downstream genes by recognizing a specific cellular effector. Although nearly 50 riboswitch classes are known, only a handful recognize multiple effectors. Here, we report the 2.60-Å resolution co-crystal structure of a class I type I preQ1-sensing riboswitch that reveals two effectors stacked atop one another in a single binding pocket. These effectors bind with positive cooperativity in vitro and both molecules are necessary for gene regulation in bacterial cells. Stacked effector recognition appears to be a hallmark of the largest subgroup of preQ1 riboswitches, including those from pathogens such as Neisseria gonorrhoeae. We postulate that binding to stacked effectors arose in the RNA World to closely position two substrates for RNA-mediated catalysis. These findings expand known effector recognition capabilities of riboswitches and have implications for antimicrobial development.

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Section: Discussionmentioning

confidence: 99%

A small RNA that cooperatively senses two stacked metabolites in one pocket for gene control

et al. 2022

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“…In particular the discovery of the many different RNA types involved in the regulation of cellular processes, such as for example siRNAs, [1] ncRNAs, [2] or riboswitches [3–5] has put demand on synthetic chemistry to provide oligonucleotides (ONs) carrying specific labels or modifications. Catalytically active ONs (ribozymes) as integral part of the RNA world hypothesis have been synthesized in variants decorated with various modifications in the context of studies regarding the origin of life [6–8] …”

Section: Introductionmentioning

confidence: 99%

“…Catalytically active ONs (ribozymes) as integral part of the RNA world hypothesis have been synthesized in variants decorated with various modifications in the context of studies regarding the origin of life. [6][7][8] It is therefore not surprising that there is an immense demand in the scientific community for methods which allow the identification, tracking and specific isolation of various ONs in vitro and in cells without interference or cross reactions with other biomolecules. Over the years many such methods, which rely on the selective and site specific introduction of modifications or reactive handles into the ONs of interest have been developed.…”

Section: Introductionmentioning

confidence: 99%

Azide‐Modified Nucleosides as Versatile Tools for Bioorthogonal Labeling and Functionalization

Müggenburg

Müller

2022

The Chemical Record

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Azide‐modified nucleosides are important building blocks for RNA and DNA functionalization by click chemistry based on azide‐alkyne cycloaddition. This has put demand on synthetic chemistry to develop approaches for the preparation of azide‐modified nucleoside derivatives. We review here the available methods for the synthesis of various nucleosides decorated with azido groups at the sugar residue or nucleobase, their incorporation into oligonucleotides and cellular RNAs, and their application in azide‐alkyne cycloadditions for labelling and functionalization.

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“…As an exception to this rule, a few DNAzymes such as HRP-mimicking G-quadruplexes have been reported, but their catalytic activity is orders of magnitude lower compared to their protein-based counterparts ( 13 , 14 ). RNA-based catalysts have also been reported, but their biological instability is a significant challenge for a wide range of applications ( 15 ). Thus, proteins remain the molecules of choice to perform enzymatic reactions, to interact with other molecules, and to functionalize nanostructures.…”

Section: Introductionmentioning

confidence: 99%

CATANA: an online modelling environment for proteins and nucleic acid nanostructures

Kuťák

Melo

Schroeder

et al. 2022

Nucleic Acids Research

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In the last decade, significant advances have been made towards the rational design of proteins, DNA, and other organic nanostructures. The emerging possibility to precisely engineer molecular structures resulted in a wide range of new applications in fields such as biotechnology or medicine. The complexity and size of the artificial molecular systems as well as the number of interactions are greatly increasing and are manifesting the need for computational design support. In addition, a new generation of AI-based structure prediction tools provides researchers with completely new possibilities to generate recombinant proteins and functionalized DNA nanostructures. In this study, we present Catana, a web-based modelling environment suited for proteins and DNA nanostructures. User-friendly features were developed to create and modify recombinant fusion proteins, predict protein structures based on the amino acid sequence, and manipulate DNA origami structures. Moreover, Catana was jointly developed with the novel Unified Nanotechnology Format (UNF). Therefore, it employs a state-of-the-art coarse-grained data model, that is compatible with other established and upcoming applications. A particular focus was put on an effortless data export to allow even inexperienced users to perform in silico evaluations of their designs by means of molecular dynamics simulations. Catana is freely available at http://catana.ait.ac.at/.

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The potential versatility of RNA catalysis

Cited by 24 publications

References 79 publications

A small RNA that cooperatively senses two stacked metabolites in one pocket for gene control

A small RNA that cooperatively senses two stacked metabolites in one pocket for gene control

Azide‐Modified Nucleosides as Versatile Tools for Bioorthogonal Labeling and Functionalization

CATANA: an online modelling environment for proteins and nucleic acid nanostructures

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